Talk:Natural product/Archive 3

Archive 1

Archive 2

Archive 3

Archive 4

Creating synthesis subsections

The current synthesis section says less about synthesis than about why things cannot be synthesized, ending with a short paragraph on partial synthesis; it currently says nothing at all about natural products total synthesis, at all (the simplest expectation for the section based on its title). I am therefore:

• creating a subsection called partial synthesis to contain that specific information,
• creating a separate subsection, yet to be populated, for material on total synthesis, and
• moving material that does not fit into these two subsections either into the section lede, or elsewhere.

In particular, the sentence on isolates not functioning after isolation because of the presence of synergies between compounds in the isolate is being moved to the Isolation section. Le Prof — Preceding unsigned comment added by Leprof 7272 (talk • contribs) 20:24, 17 May 2014 (UTC)

Natural product journals

For discussion, in re: an eventual outline for this article, here are the indicated topical areas of coverage for two top journals on natural products, NPR, impact factor 10.2, and Journal of Natural Products, impact factor 3.3:

• see [1] and [2], respectively.

For discussion, in re: an eventual outline for this article, here is the indicated topical areas of coverage for two top possible journals on pharmacognosy, Phytomedicine, impact factor 3.3, and Pharmacognosy magazine, impact factor 1.5:

• see [3] (then click on "View full aims and scope") and [4], respectively.

Note, this is not a thorough or complete approach, but it gives a sampling of the range of biological and chemical topics covered in 4 reputable journals. Note, impact factor is a poor criterion for selection, because of its lack of availability for many journals, and its inherent biases. Nevertheless, it is a ready and objective criterion that allowed this presentation to proceed. Le Prof Leprof 7272 (talk) 04:57, 19 June 2014 (UTC)

Article scope

Here are the scopes of the journals mentioned below, to save the hard work of looking to those links, to see what most scientists mean when they refer to natural products research:

"Natural Product Reports (NPR) is a critical review journal which stimulates progress in all areas of natural products research including isolation, structural and sterochemical determination, biosynthesis, biological activity and synthesis. The scope of the journal is very broad and many reviews discuss the role of natural products in the wider bioinorganic, bioorganic and chemical biology communities. Areas covered include enzymology, nucleic acids, genetics, chemical ecology, carbohydrates, primary and secondary metabolism and analytical techniques. NPR articles are designed to give an interesting insight into the topic, focussing on the key developments that have shaped a field rather than giving a very comprehensive overview of all results. Authors are encouraged to include their own perspective on developments, trends and future directions. A link to example articles in each key topic area can be found at the bottom of this page." See [5] and [6].

"The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred." See [7] and [8].

Perhaps compare this scope (and motivation) as a reliable source, to the trade source cited above, whose influential material currently helps guide this article. These scope statements are what define, 95% for me, what I think the scope and priorities that this NP article should capture. Not my own opinion, but the opinion of the experts in the field of natural products research. No more caricatures. Fight with this. Show me the focus of reputable sources like this, and not web pages and stray lines from one book. Then I might be persuaded toward "cell and leaf and, oh yes molecules too" definitions/classes of natural products. Le Prof Leprof 7272 (talk) 23:24, 19 June 2014 (UTC)

"Drugs" section

Two questions: 1) Do we really need 48 of the same reference repeated over and over again? Can't we simply reference the introductory sentence and leave it at that? 2) Do we even need this section? How is this listing of 48 drugs, with no other contributing information, not WP:TRIVIA? Padillah (talk) 17:33, 13 June 2014 (UTC)

(1) Agreed, we do not need 48 examples. This list can be trimmed considerably. (2) Disagree. This is an important section that establishes the notability of the entire article. I suggest that this bulleted list be trimmed and converted into prose. Furthermore the individual examples to should be restricted to drugs that have particular historical importance and are representative of diverse chemical and therapeutic classes. Boghog (talk) 20:21, 13 June 2014 (UTC)

@Padillah, thanks for visiting. I agree with Boghog as to need for a solid section here, but agree with what I perceive you to be saying, that there are questions/problems with the current list-only approach. There at least needs to be introductory prose, e.g., establishing whether NP drugs are a significant or insignificant component of market and therapeutic arsenal. (Significant is true.) Whether in the end the list should be comprehensive, versus citing a source that is, and focusing on current on-market examples meeting a particular cutoff criteria, these are matters for further discussion. Another issue, again as I perceive you noticed, is the fact that the citation appearing for almost all, a holdover from the early days of this article, is not the best or most up to date source for this at this point in time. Bottom line, agree, that this is one aspect of the current article that needs committed attention. Anything else you want to comment on? Cheers. Le Prof Leprof 7272 (talk) 01:36, 14 June 2014 (UTC)

OK, so let's start with the first sentence:

"A number of drugs have been derived from biological a source in nature"

Is that supposed to say "...derived from a biological source..." or "...derived from biological sources..."? Padillah (talk) 14:28, 16 June 2014 (UTC) P.S. I don't care who makes what suggestion as long as it's a good one. I will not discuss editors or their motives. Only edits. PERIOD.

 Fixed Yes as you suggest, it should read "...derived from biological sources...". I am busy in real life, but should have time this weekend to work on this section. Cheers. Boghog (talk) 14:44, 16 June 2014 (UTC)

OK, I think there is general agreement that this section should be trimmed, turned into prose, and the sources updated. At the same time, I think it would be useful to transfer the information in the current version of this section into a stand alone list. I have started working on a draft here (note that a table would replace the bulleted list). Thoughts? Boghog (talk) 10:02, 20 June 2014 (UTC)

Resolution of conflict

The scope of this subject is slightly wider than science, it also includes traditional medicines and consumer products, hence including "non-scientific" citations is fair game. Boghog (talk) 20:55, 19 June 2014 (UTC)

To be clear, in your view, this Natural Products article should be

• broader than chemistry (to biology, agreed),
• and should include "traditional medicines (agree in principle, but note that such a section, wholly unreferenced, already appears on this, though there is no section on FDA/EMA-approved drugs, hence unbalanced tag),
• and you add consumer products? Based on a citation from a commercial trade group promoting things they term "natural product", to support advancing industry interests for sale of products that benefit by association with the "natural products" moniker? A foundation that is lead by these esteemed independent, non-self interested parties: [9]? And a foundation that presents its perceptions of what natural products are on such pages as these: [10] (note the esteemed reference, "What color is your diet?"), [11] (note repeated "ND" credentials in authorship), [12], [13], [14], etc.

Tell me again why you dropped "foods" and "probiotics" from your classes of natural products, alongside whole organisms and leaves? Surely there is room for these two additional classes/categories, from such a fine source. Le Prof Leprof 7272 (talk) 22:15, 19 June 2014 (UTC)

Instead of assigning blame, focus on improving the article. I agree that many of the health claims made about "natural products" are suspect (but after the Dietary Supplement Health and Education Act of 1994 are allowed in the US). But that is not the issue. The issue is how the term "natural product" is used. These "natural products" are widely marketed to the general public at least in the US. Therefore the general public is exposed to this definition of the subject and hence it is appropriate to mention this use of the term this article. Perhaps a better source can be found and I am open to suggestions. Regardless of whether this definition is in-scope or out-of-scope, it is appropriate to mention it in the lead (per Scope, ... it may be necessary to identify material that is not within scope.). I also agree that we need to add sources to the traditional medicines section. Boghog (talk) 11:31, 20 June 2014 (UTC)

@Boghog, Perhaps we are finally making needed progress. Thank you for acknowledging the need for changes. Yes, we agree that the long reference-less "traditional medicine" (T M) section needs citations. Q1 Can you also allow, that in this section's editing, it may need changes, both to possibly shorten, and in cases where the material present does match the best available secondary sources? Then, Q2 Can you also allow that the existence of the TM section—synonymous with indigenous or folk medicine here at WP, and lumped with alternative medicine by the WHO) makes the article unbalanced, as long as it lacks a section on NP therapies in modern medicine (so that we clearly need this new section)? And to make further progress on the issues in the Classes section: Toward your desire of non-chemistry representation, I'd note, there is plenty of acceptable non-chemistry within the valid scope of natural products study, see here [15]. This material can and should be expanded. You admit that the organisms and leaves definition is "only mentioned in passing" and is there to "put the subject of natural products in context", and that "we could rephrase it to down play it as a definition". Thank you. I would propose that organisms and leaves as NPs be mentioned in a closing section of the article, along with commercial definitions and aspirations, and that these translate to a sentence in each of the lede and the Classes section (a closing rather than prominent mention in each).

There then remain two further matters: You elevated and still defend a prominent, purely commercial and decidedly minor connotation of the NP term—a connotation for which no journal or real secondary source exists—and this contributes further to opening bias in the article, away from its most prevalent meanings and connotations, to fringe meanings. These deserve mention, but not the prominence you give them. Q3 Can we agree that this commercial "definition" can, until substantial secondary support be found, also be "rephrase[d]... to down play it as a definition"? FInally, and most critically, Q4, can you also acknowledge that someone besides you can make changes, without risking reversion? Please reply to these four specific Y/N questions as you wish. @Smokefoot, @V8rik, @Padillah, @Doc James, please attend to the possible closing answers to this long debate. (Others still interested, invited as well.) Le Prof Leprof 7272 (talk) 15:15, 20 June 2014 (UTC)

I would also note the option, that just as the connotation of "steroid" to mean "anabolic steroid" is dealt with at the Steroid article—with hatnote to redirect to a separate article—that the marginal (though promoted and so emerging) commercial connotation of natural product as probiotics, foods, dried leaves and twigs, naturapathic remedies, honey and bee stings, etc. could in a philosophically consistent way be separated into a separate article such as "natural products (commercial)". How might this fit? Le Prof Leprof 7272 (talk) 15:22, 20 June 2014 (UTC)

Good, there seems to be grounds for agreement here. There also seems to have been some misunderstanding, especially concerning the traditional medicines section. I never disputed this or other sections of the article needed to be improved and of course we can add new sections to balance the article if required. My main concern was the overall scope of the article. But that potential misunderstanding is not so important. What is important is how we move forward. In response to your specific questions:

1. Traditional medicines section – of course this section needs to be carefully sourced and if reliable sources cannot be found for any statement in the current section, that statement should be removed.
2. We need to add an "applications to modern medicine" section to balance the traditional medicines section. I see these sections as nicely complimenting each other as there are many examples of traditional medicines that have been used as starting points for modern drug discovery.
3. The commercial use of the term natural product may be considered a borderline in-scope/out-of-scope definition. As I have already stated, even if it is out-of-scope, per scope it would still be appropriate to briefly mention it in the lead to define the scope of the article.
4. No one, myself included, owns this or any other article. I or others may disagree about certain edits, but these disagreements should be worked out on the talk page. Boghog (talk) 16:25, 20 June 2014 (UTC)

Great. See outline appearing below, for discussion. Le Prof Leprof 7272 (talk) 17:39, 20 June 2014 (UTC)

Potential Good general sources for the article

• Füllbeck M, Michalsky E, Dunkel M, Preissner R (2006). "Natural Products: Sources and Databases". Nat Prod Rep. 23 (3): 347–56. doi:10.1039/b513504b. PMID 16741583.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Mander L, Liu H-W, ed. (2010). Comprehensive natural products II chemistry and biology. Vol. 1. Oxford: Elsevier Science. ISBN 978-0-08-045382-8.

Le Prof Leprof 7272 (talk) 17:53, 22 June 2014 (UTC)

• Rostagno MA, Prado JM, ed. (2013). Natural Product Extraction: Principles and Applications. Cambridge, UK: Royal Society of Chemistry. doi:10.1039/9781849737579. ISBN 1849736065.

Le Prof Leprof 7272 (talk) 18:39, 22 June 2014 (UTC)

Call for sources for history section

Here are some that I have found thus far. Best would be as yet-unidentified scholarly "History" chapter or section in a book on NPs (that can be summarized), with the following adding additional colour:

• Dias DA, Urban S, Roessner U (2012). "A historical overview of natural products in drug discovery". Metabolites. 2 (2): 303–36. doi:10.3390/metabo2020303. PMID 24957513.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
• Newman DJ, Cragg GM (2012). "Natural products as sources of new drugs over the 30 years from 1981 to 2010". J. Nat. Prod. 75 (3): 311–35. doi:10.1021/np200906s. PMC 3721181. PMID 22316239. (updates 3 earlier reviews, 2007, 2003, and 1997) This is also a crucial article, for it reflects categorizations of the very broad area by thought leaders in this area.
• Ji HF, Li XJ, Zhang HY (2009). "Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia?". EMBO Rep. 10 (3): 194–200. doi:10.1038/embor.2009.12. PMC 2658564. PMID 19229284.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• McChesney JD, Venkataraman SK, Henri JT (2007). "Plant natural products: back to the future or into extinction?". Phytochemistry. 68 (14): 2015–22. doi:10.1016/j.phytochem.2007.04.032. PMID 17574638.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Peláez F (2006). "The historical delivery of antibiotics from microbial natural products--can history repeat?". Biochem. Pharmacol. 71 (7): 981–90. doi:10.1016/j.bcp.2005.10.010. PMID 16290171.

For those interested in the evolution of the concept in chemistry, here is a nice, long tome on the beginnings of the Nat Prod Gordon Conference that began as a meeting on steroids:

• Michael Smith. "The Natural Products Gordon Conference. 1951-2011" (PDF). University of Connecticut.

Please submit other historical references. Needed is to find coining of term, and articles on history of non-chemical concepts (where histories relating NPs to drug discovery are clearly most prevalent).

Le Prof Leprof 7272 (talk) 19:12, 22 June 2014 (UTC)

Natural product as irrelevant adjectival construction

In looking for the first coining of the term "Natural product", I came across this discussion of Priestley's oxygen studies:

"Dr. Priestley, the father of the late improvements in chemistry, seems to be wedded to ancient systems. He finds that with the water obtained by the inflammation of oxygen and hydrogen gases, there is always mixed a small portion of acid, commonly nitre ; and he thence infers that this is the real and natural product of the combination." from Phil. Trans. Royal Soc. London, 1790 (full citation on request)

It is a very early use of the article title term, before its modern evolution, that is an example of the juxtaposition of the two terms as adjective and noun, with no relation to modern meaning. (There are continuing, though diminishing, uses of the same type of construction in modern literatures, today, and much wider web-based appearances. I hesitate to call the latter NP sources.)

Le Prof Leprof 7272 (talk) 19:17, 22 June 2014 (UTC)

Propose removal of this paragraph as belonging in another article

The following paragraph is on the difficulty of obtaining information from Traditional Medicine practitioners, based on anecdotal accounts in books. I believe this topic, currently 6 sentences and a third of the Trad Med section, may demand at most one sentence in this article (though this text may fit in a the Trad Med article per se):

It can be challenging to obtain information from practitioners of traditional medicine unless a genuine long term relationship is made. Ethnobotanist Richard Schultes approached the Amazonian shamans with respect, dealing with them on their terms. He became a "depswa" - medicine man - sharing their rituals while gaining knowledge. They responded to his inquiries in kind, leading to new medicines. On the other hand Cherokee herbalist David Winston recounts how his uncle, a medicine priest, would habitually give misinformation to the visiting ethnobotanists. The acupuncturists who investigated Mayan medicine recounted in Wind in the Blood had something to share with the native healers and thus were able to find information not available to anthropologists. The issue of rights to medicine derived from native plants used and frequently cultivated by native healers complicates this issue.

and for both, the sources demanded are reliable, scholarly secondary sources. First hand accounts of experiences, whether anthropological or popular, are primary sources, and not what is needed here. The re-location of the paragraph to Talk is intended to persist until the ultimate fate of the material can be decided based on editor discussion. Until it is, its presence off-point content adds to the article's imbalance (as the article still lacks a section on NPs in Western, evidence-based medicine). Le Prof Leprof 7272 (talk) 10:04, 1 July 2014 (UTC)

References

Proposed article outline

Here is a formal proposal, merging the current article structure with ideas from the discussion, and from the most prominent sources. Note, every attempt was made to consult Boghog sources (e.g., Samuelsson), as well as to incorporate common biological themes from there and from the most highly regarded natural product journals. I have not made an attempt to capture all current article content; the lists appearing should be considered examples, and not as being complete/exhaustive, and should not be construed as a suggestion to remove any valid content appearing in the article. Finally, note, Sections already appearing are underlined. sections appearing and proposed that are also in major natural products journals are indicated in bold, and sections or subsections appearing or proposed that also appear in Samuelsson are italicized.

Proposed Article Outline

I Classes Based on biosynthesis Primary metabolites (including saccharide areas) Secondary metabolites (introduction only, breakdown to appear under structure) Other Based on structure (see Biosynthesis and enzymology section for possible breakdown) Based on source (essentially a brief systematic summariy of sources appearing in the current "Natural sources" section, so phrases "marine NP", "fungal NP", etc, have meaning going forward) II History (parts of what are now in the impact on chemistry, but mostly new, from a richly sourced literature, including significant societal impacts) III Medical uses Traditional medicine and ethnopharmacology Modern pharmacotherapy On-market drugs Oncology Infectious disease Other areas Off-market examples IV Natural sources Introduction (including discussion of difficulty of assigning single organism sources in commensal and other cases) Microorganisms Fungi Plants and Animals Terrestrial Marine (dividing current sections thus, removes issue of animals, plants having two possible locations in current outline, and having venom and toxins similarly confounded as to location; bottom line, a simpler basis of categories than the current is proposed) (propose need for substantial shortening of this section, to not overwhelm developing article, and to allow room for biological functions, examples) V Biological functions Introduction As transporting agents In regulatory signaling (hormonal) roles As signals effecting differentiation As agents integrated into sporulation As agents of symbiosis As competitive weapons (tentative, based only on Demain and Fang thus far) VI Important examples microbial antibiotics microbial mycotoxins plant semiochemicals plant colorants Etc., etc. (familiar or societally impactful cases, from red tide to yew needles) VII Biosynthesis and enzymology Primary metabolism (including energy storage/sacchharide areas, done first so that secondary glycosides have context) Secondary metabolism From Shikimate (done early so mixed origin classes can include shipmate derived components) From acetate Acylpolymalonates (incl. prostaglandins, polyketides incl. mixed, macrolides, etc.) Isoprenoids (incl. all terpene classes, steroids, calciferols, etc.) From amino acid pathways Alkaloid pathways Purine and Pyrimidine pathways (including other nucleic acid topics) Other pathways VIII Genetics and evolution Proposed alteration to outline. Le Prof Leprof 7272 (talk) 06:20, 23 June 2014 (UTC) IX Isolation, purification, and analytical techniques Sources and preparation Crude extracts (can include and wikilink to herbal remedies) Purifications Analyses X Structure and properties Structure determination Property determination XI Biological activities screening type assays, incl. HTS individual compound assay pharmacologic evaluation tool compound use toxicology XII Commercial production Via harvest Via biotechnology Microbial (incl. fermentation) Plant tissue Semisynthesis Other XIII Discovery chemical synthesis Microbial transformations Semisynthesis Total synthesis Combinatorial synthesis and biosynthesis XIV Research and teaching Pharmacognosy Chemical ecology Ethnopharmacology Chemistry (including remaining aspects of current "Impact on chemistry" section) Other areas (to include phylogenetics, systems biology, and chemoinformatics, as described in Sammuelsson) XV Other commercial aspects (including legal definitions and regulations)

Discussion

Please use a colored text to place in edits/additions, and sign below me in the same colored text? Le Prof Leprof 7272 (talk) 18:20, 20 June 2014 (UTC)

Le Prof, thanks for your positive reply and constructive suggestions. I am busy in real life today, but I should be able to respond in more detail over the weekend. Cheers. Boghog (talk) 18:57, 20 June 2014 (UTC)

The overall outline is good, but I think it is bit too ambitious to start with. Rather than trying to tackle the entire article at once, I think it is more realistic and practical to deal with one section at a time. Also per TenOfAllTrades previous comments, I will not be adding any additional color highlighting to this talk page. I request that we keep the formatting of this talk page clean and simple.

I suggest that we start with the classes section. One immediate reaction that I have is that the distinction between primary and secondary metabolites is not synthetic, but functional. Hence the I believe the first subheading should read "Based on function" instead of "Based on biosynthesis". Boghog (talk) 19:47, 21 June 2014 (UTC)

On the specific change: biosynthesis is a relatively simple-to-use, widely agreed upon framework that is one of two that appears in all texts I consulted (the other is structure class, which is a narrower subset, e.g., prostaglandins). Functions of natural products are often unknown (is the molecule an antifeedant, an effector in signal transduction pathways, a semiochemical, etc.?), so subject to change with emerging research results, and, more critically, functions are subject to intense research debate. (I have been there.) I think there is a reason why texts use biosynthetic pathway as the way to categorize. If near any scientist can look at brevetoxin or endiandric acid and get correct the general pathways by which it is biosynthesized, the field is mature enough to rely upon. And, it will provide a framework simple for non-specialists to use, in bringing material in direct from sources (so we don't end up with an article of one sentence paragraphs or subsections. (As a sidebar, I'll say that the molecule I worked on in graduate school began as a critical intracellular signal molecule, and ended 3 years later as having no known function—when the first conjecture proved incorrect.) More about editing path forward after dinner. Le Prof Leprof 7272 (talk) 00:09, 22 June 2014 (UTC)

There are four (and possibly more) frameworks for classifying natural products: (1) what they are – their chemical structure, (2) why they made – their function, (3) how they made – their biosynthesis, and (4) where do they come from – their source. Primary vs. secondary metabolite classification falls within framework #2, not #3. The functional distinction between primary and secondary metabolites is already made clear in the present version of this article as well as the specific articles on primary and secondary metabolites. Primary metabolites have an intrinsic "survival" function while secondary metabolites have an extrinsic "ecological" function. It is true that the specific function of many secondary metabolites is currently unknown, but one thing that is clear is they are not required for the "normal growth, development, and reproduction" of the organism. Hence the subsection that concerns primary vs. secondary metabolites should read "Based on function" instead of "Based on biosynthesis". Boghog (talk) 06:37, 22 June 2014 (UTC)

Here is a good review of the functions of secondary metabolites: PMID 11036689 This review list several other functions of secondary metabolites (symbiosis, pheromones, and transport agents) that we should probably add the natural product article. Boghog (talk) 07:15, 22 June 2014 (UTC)

Below are basic functional definitions of primary and secondary metabolites that are consistent with the ones used in the current article:

Primary and secondary metabolite definitions

Kliebenstein DJ (2004). "Secondary metabolites and plant/environment interactions: a view through Arabidopsis thaliana tinged glasses". Plant, Cell and Environment. 27 (6): 675–684. doi:10.1111/j.1365-3040.2004.01180.x. In 1891, following Stahls work on plant biochemistry, Kössel suggested a distinction between basic and secondary metabolism (Stahl 1888). Basic metabolism refers to the anabolic and catabolic processes required for respiration, nutrient assimilation, and growth/development, namely those processes required for cell maintenance and proliferation. In contrast, secondary metabolism refers to compounds present in specialized cells that are not necessary for the cells survival but are thought to be required for the plants survival in the environment. These compounds are believed to aid plant fitness by preventing insect herbivory and pathogen attack as well as aiding reproduction through providing pollinator attraction as either floral scent or coloration. Karlovsky P (2008). "Secondary metabolites in soil ecology". Soil Biology. 14: 1–19. doi:10.1007/978-3-540-74543-3_1. More than a century ago, Kössel (1891) defined secondary metabolites by exclusion (compounds that do not belong to primary metabolites), provoking criticism which has never ceased. The current, generally accepted concept in line with Kössel's view is that primary metabolites are chemical components of living organisms that are vital for their normal functioning, while secondary metabolites are compounds which are dispensable. A distinguishing feature of secondary metabolites is that their production is limited to a group of species or genera and is rarely conserved over a wide taxonomical range, while primary metabolism is conserved among phyla and across kingdoms.

This may be an easy exchange. First, see the revised outline above. Second, your categorizations are consistent with mine—I mentioned two (your 1 and 3), omitted 4 because it's already in the article and outline twice (and so not contended). Here, this is what we are talking about: See portion of outline above, Heading "Classes" and 10 lines following, through "(essentially a brief systematic...".

This proposed outline section leaves your classes in place, but by function we mean different things. And—with a wave of hand (for this one is almost too easy to get past)—the issue over your number 2 may well disappear, because I misunderstood you in your brevity (and you me... for my brevity?).

Look back to the "functions" I list and object to (antifeedant, signal transduction effector, a semiochemical, etc.) and look to the "functions" you promote (primary and secondary metabolites). I was subsuming the metabolisms under the moniker of biosynthesis; it seems you want to subsume biosynthesis under the moniker of metabolisms. I have no strong opinion whatsover, except that whichever is done, it's the preponderant view in secondary sources and good, advanced textbooks. Otherwise, of course I agree with your principles.

I propose two things, based on the nice Demai-Fang review. First, function, as these authors define it (and I refer to it with the semiochemical and signal transduction examples) deserves a full section to itself (see revised outline of today). Second, the two forms of metabolism are already in the outline, and I propose no change (I affirm the importance in distinctions you argue). The only remaining issue is semantic: your way of using the word "function" here as the subheading. When you look at how the word function is used in the 2° NP literature such as the Demai-Fang article, it hones close to mine: see also [16] and [17] and Chapter 2 here [18], etc. etc. Bottom line: Can you accept this topical area as needing its own section, and then suggest a different subheading word over primary and secondary metabolism? Perhaps "By type of metabolism" (as metabolism is more specific than function, and encompasses the biosynthetic categories that will have to appear under "Secondary metabolism").

Does this fly for you—that there is only a semantic issue, and nothing substantial, and that something besides "function" might work as the subheading? Le Prof Leprof 7272 (talk) 17:00, 22 June 2014 (UTC)

Thanks for your reply. Of course, the biosynthesis of secondary metabolites use the products of primary metabolism as starting materials. So from that standpoint, primary vs. secondary metabolites could be covered under biosynthesis. However that is not how the concept of primary vs. secondary metabolites was originally defined nor is currently used. What I am suggesting is that we place biosynthesis and function on equal levels so that neither is subsumed by the other. This is done for example in:

• Gutzeit HO, Ludwig-Müller J (2014). Plant Natural Products Synthesis, Biological Functions and Practical Applications. Weinheim: Wiley-VCH. ISBN 3527332308., Chapter 1: Biosynthesis and chemical properties, Chapter 2: Function, Section 2.1: Secondary compounds in primary metabolism

Also since structure and biosynthesis are so interrelated, perhaps both should be covered in the same section, similar to the way they are covered in:

• Dewick PM (2009). Medicinal natural products: a biosynthetic approach (3rd ed.). Chichester: Wiley. ISBN 0470741678.
  • acetate pathway → fatty acids and polyketides
  • shikimate pathway → aromatic amino acids and phenylpropanoids
  • mevalonate methyletrythritol phosphate pathways → terpenoids and steroids
  • amino acids → alkaloids

Boghog (talk) 06:15, 23 June 2014 (UTC)

I agree with all of this, but we are talking past each other—see my proposal for change to the outline. I am speaking of functions that have nothing to do with biosynthesis or metabolism. I am using function as used by Demai-Fang article (and those now included in a separate section of the article), also in [19] and [20] and Chapter 2 here [21], etc. etc. These are the "functions" that we always were referring to, when we used this f-word. Note also, all of what you are getting at with the Dewick citation appears in similar form in the proposed (later) "Biosynthesis and enzymology" section. Of course, the descriptions in the "Classes" and "Biosynthesis and enzymology" sections will have to match up. Cheers. Le Prof Leprof 7272 (talk) 06:29, 23 June 2014 (UTC)

Sorry to be so insistent on this, but please loose the text shading. As previously mentioned by TenOfAllTrades and Padillah, it is distracting, confusing, and unnecessary. I can easily figure out what is new without it.

Also I do not see why we cannot have a short function section under classes that includes the functional distinction between primary and secondary metabolites. At least some sources in the literature (e.g., Gutzeit & Ludwig-Müller) have a similar organization. Boghog (talk) 06:49, 23 June 2014 (UTC)

For the sake of discussion:

Alternative classes outline

Classes Based on function Primary metabolites intrinsic function mainly affecting the organism that produces them associated with essential cellular functions such as respiration, nutrient assimilation, and growth/development components or products of fundamental metabolic pathways or cycles that are essential for life widely distributed throughout each of the kingdoms of life includes carbohydrates, lipids, proteins, and nucleic acids Secondary metabolites extrinsic function mainly affecting other organisms species specific and dispensable however increases the competitiveness of the organism within the environment includes the major strutural classes listed below Based on biosynthesis/structure acetate pathway → fatty acids and polyketides shikimate pathway → aromatic amino acids and phenylpropanoids mevalonate methyletrythritol phosphate pathways → terpenoids and steroids amino acids → alkaloids Based on source bacterial/archaeal eukaroyotic plant fungi animal

Boghog (talk) 18:58, 23 June 2014 (UTC)

Sorry, we are talking past each other again—you seem to be responding more to your own thoughts that crop up when you read my opening sentence, than to the gist of what I say, or the particulars of what I ask. I am at a loss as to how to move you past doing this, but I will try one more time.

First, I offered a proposal for a new section, on "Biological functions" of NPs, and reordered some sections in the initial outline proposal, as a possible way the new section might best fit into the flow of the article. I called your attention to it with the sentence, "...see the revised outline above." and by shading the revised portion of the original outline. You have not responded to this. Please do. (Q1)

Next: Three times said, I agree that primary and secondary metabolisms together constitute a category. Same, three times, that a multitude of sources use the term "function", not as an overarching word to cover metabolisms, but to cover the one to several functions that NPs serve in the organisms they are produced in (to say a fourth time, e.g., antifeedants, cofactors, semiochemiacals, secondary messengers, structural elements, feedback inhibitors, etc.). So, three times I've asked you to come up with an alternate term, so that the word "function" can be used in the way I see it used in most sources. And so, for a fourth time: there is no fundamental issue here, just this need to make a choice of a term copacetic with how it appears in most sources. Can we now address this head on, and say we will call this category "based on type of metabolism" or "based on metabolism" (or some other phrase of your choosing), and get past this semantic issue? (Q2)

Then, I have no opinion yet on combining biosynthesis and structure in the classes section. I think there is an argument for keeping them separate, but I will think about this further. If you have further sources other than Dewick, post them, and I will review them too (Q3).

Finally, I'll likely agree with the intrinsic/extrinsic, dispensable/indispensable, narrowly distributed/widely distributed dichotomies, on two conditions: that they are communicated as pedagogic generalizations and not hard rules (because the dichotomies have explanatory value greater than evolutionary/theoretical substance, and because as a teaching academic, counter-examples come to mind). So, if its "most steroids without ring scissions are rigid", we will be fine. If its "steroids are rigid", we'll have trouble. Which will it be? (Q4)

In closing, some housekeeping. Please, again, insert your proposed Classes revision into the broad outline, so it is all in one place. (Use temporary color or shading, or a diff link as you please, to call my attention to what you change.) Otherwise, the Talk will get longer and longer with outline snippets, and they will be hard to refer to in discussion (because they will numerous and in different locations). Paste it in, please. Then, feel free to remove my shading from the outline, after it's served its purpose (calling your attention to the change for which I've asked your response). More generally, highlights, colors, all these are tools of communication. If they are not needed, they will be dispensed with. I too will be glad when this can happen, but as long as I am ignored, talked past, it will be used, at least transiently, to try to get your attention. Finally—and I sincerely hope this is not the case, but it's been suggested to me—if your earlier ignoring of Q1 and Q2 is your way of guiding me instead to deal with what you wish... it isn't going to work. No editor controls other editor's interests/editing. (E.g., I've not and will not agree to limit editing to the classes section.) I'll engage you, going forward, on your editorial interests to the extent that you engage me on mine. Le Prof Leprof 7272 (talk) 01:29, 27 June 2014 (UTC)

Both this discussion and the outline are getting way too complicated. Keep the discussion focused on natural products.

Regardless of how the rest of the article is organized, I think it is essential that we include a section on the functional distinction between primary and secondary metabolites. The lead already mentions this, but there should be nothing in the lead not discussed in more detail in the body of the article. In answer to your questions:

• Q1: Function section – The functions listed in your outline fall almost entirely under secondary metabolites. I suggest that we merge my proposed function section with yours. The first division would be between primary and secondary metabolites. Under primary metabolites, we list the major cellular functions (energy, structure, and information) and what types of substances are used for each (respiratory and photosynthetic enzymes; cell membranes and walls; nucleic acids). Under secondary metabolites we include your list (except for hormones which are classified as primary metabolites).
• Q2: Semantic issue of section heading – If the function section includes precise definitions of primary and secondary metabolites, then I would accept having second section on biosynthesis with a split between primary and secondary metabolites.
• Q3: Structure and biosynthesis – I believe that since structure and synthesis are so interrelated, it would make sense to combine the two into a single section as Dewick does.
• Q4: Definitions – I believe that in order to put the subject in perspective, it is useful to include a broad description of what a natural product is. At the same time, we can point out that natural products within the fields of organic and medicinal chemistry normally have a more restricted definition. Boghog (talk) 08:33, 29 June 2014 (UTC)

Q0: "Keep the discussion focused on natural products." Unnecessary and insulting. Keep such to yourself. If you answered direct clear questions, there would be no need for attempts at persuasive language to urge you to stop doing so. No reply needed to this. Now, for the rest, refer back to the original questions, because for the most part you again left them unanswered (see section with Q1, Q2, etc. labels above).

lpQ1: Question missed, and so unanswered. You say, "I suggest that we merge my proposed function section with yours." The only outline section you have presented is the bullet-style, early Classes section, Section I. My question regards a proposed Section V (see outline), a full section, a few hundred words, to fully elaborate various functions of NPs. Clearly, later full sections of information cannot be subsumed into the brief, early, organizational, bullet-style Classes section (though the relationship and organization of the Classes and other sections should be consistent). So question Q1 remains: what of the proposed placement and content (see outline) of the new full section, Section V, "Biological functions". Heard and acknowledged it should be complete, and parallel the outline in Section I, Classes. Anything else?

lpQ2: You answered a question not asked (is it OK to have section like Section VII), and did not answer the question asked (can we rename the indicated "function" class within Section I, Classes). Asking same question, no alteration, fifth time. Look back to Q2, and reply to my actual question, please.

lpQ3: You answered a question not asked (should there be separate structure and biosynthesis sections), and did not answer the question asked (are there further sources besides Dewick giving the proposed content organization?). Look back to Q3, and reply to my actual question, please.

lpQ4: Completely misses/does not address specific question of how the primary and secondary metabolite dichotomies you give in your as yet-unintegrated mini-outline will be presented in the article. Look back to Q4, and reply to my actual question, please.

Q5: Added, since you ignored the entire last paragraph. Insert "Will you..." in front of "Please, again, insert..." to make this a question, and answer this in next reply.

I intentionally waited a long while before looking back at this, to give you time to respond to the specific questions. I can have nothing more to say on your comments until questions already asked are actually addressed. Note, I will begin editing in small ways before this comes to fruition. To wait for full consensus on the outline may result in our obits being filed before this article becomes presentable. Le Prof Leprof 7272 (talk) 09:31, 1 July 2014 (UTC)

While my answers may be guiding, your questions are leading. In order to make progress, let's take one question at a time. In my answer to Q1, I implicitly agreed to your proposal to have a separate function section but extended the proposal to merge your function section with mine. Do you accept this compromise proposal or not? Boghog (talk) 10:13, 1 July 2014 (UTC)

In an attempt to move this discussion forward, I have placed a revised outline in the following subdirectory:

• Talk:Natural product/Outline

As I proposed above, this version merges our two function sections. I have purposely removed the underlining since it should be obvious which parts of the outline already have sections in the article. Please feel to modify. I can use the article history to compare versions. Boghog (talk) 20:06, 7 July 2014 (UTC)

Arbitrary break

Concerning the proposed outline, I think the following should be kept in mind:

• sections appearing and proposed that are also in major natural products journals are indicated in bold

Wikipedia is not a scientific journal. There is no requirement that the organization of Wikipedia scientific articles must follow the organization of scientific journals. All verifiability requires is that content must be support by reliable sources. Verifiability says nothing about how that content is organized.

Direct answers to questions posed above:

• Q1 what of the proposed placement and content (see outline) of the new full section, Section V, "Biological functions" – I think the proposed (I) classes section in the outline is problematic because it is confusing. Variants of the same biosynthetic pathway with minor modifications can be used to produce either primary or secondary metabolites. The same can be said of each of the major chemical classes of natural products. Some saccharides are primary metabolites while other saccharides are secondary metabolites. I know that I am repeating myself, but the primary/secondary metabolite division is functional, not synthetic. Trying to divide biosynthesis into what are essentially two different functional classes makes no sense whatsoever. Most major biosynthetic pathways would end up being assigned to both classes. The primary/secondary metabolite division should instead be included in the (V) biological function section.
  • The only outline section you have presented is the bullet-style, early Classes section, Section I. – A complete merged outline proposal may be found here. Note that bullet points only occur in the proposed outline and not necessarily in the article. These bullet point would be converted as much as possible into prose.
  • Clearly, later full sections of information cannot be subsumed into the brief, early, organizational, bullet-style Classes section – that depends on how big these subsections become. I would agree that as subsections, the subsections should be kept relatively brief. I would instead propose promoting all three of the class subsections to full sections and briefly mention the three classification schemes in the lead. An additional advantage of promoting these subsections is that it would reduce redundancy. And as I have already indicated above, bullet points should be converted into prose wherever possible. Boghog (talk) 11:26, 10 July 2014 (UTC)
  • When you look at how the word function is used in the 2° NP literature such as the Demai-Fang article, it hones close to mine – The scope of the review by Demain and Fang is restricted to secondary metabolites. The scope of this wikipedia article includes primary metabolites which also have functions. Hence the function section of this article should include both primary and secondary metabolites.
• Q2 is it OK to have section like Section VII - it is OK to have a section like VII, but for the identical reasons stated above in my answer to Q1, the primary/secondary metabolism headings should be removed (as is done here).
• Q3 are there further sources besides Dewick giving the proposed [merged biosynthesis and structure] content organization? Here are two additional sources:
  • Torsell KBG (1997). Natural product chemistry: a mechanistic, biosynthetic and ecological approach (2^nd ed.). Stockholm: Swedish Pharmaceutical Society (Apotekarsocieteten) in association with Taylor & Francis. ISBN 9186274635., see in particular chapters 3–9. While some natural product structures are introduced earlier (chapters 1–2), most natural products in the book are introduced along with their biosynthesis (chapters 3–9).
  • Stanforth SP (2006). Natural product chemistry at a glance (1st ed.). Malden, Mass.: Blackwell Pub. ISBN 1405145625. Essentially the entire book is organized around biosynthesis.
• Q4 So, if its "most steroids without ring scissions are rigid", we will be fine. If its "steroids are rigid", we'll have trouble. Which will it be? You already answered it best in Q0: unnecessary and insulting ;-) Boghog (talk) 12:12, 10 July 2014 (UTC) One can make a legitimate case that "steroids with ring scissions" are no longer steroids (see this discussion). Boghog (talk) 11:00, 12 July 2014 (UTC)

Preexisting total synthesis content

…moved here, so there is an easily accessible source of the prior text for other editors to consult, and so I can review to figure out what of it is of longterm value:

Not all natural products can be fully synthesized and many natural products have very complex structures that are too difficult and expensive to synthesize on an industrial scale. These include drugs such as penicillin, morphine, and paclitaxel (Taxol). Such compounds can only be harvested from their natural source – a process which can be tedious, time consuming, and expensive, as well as being wasteful on the natural resource. For example, one yew tree would have to be cut down to extract enough paclitaxel from its bark for a single dose. Furthermore, the number of structural analogues that can be obtained from harvesting is severely limited. Partial or semisynthetic procedures can sometimes get around these problems.

References

Le Prof Leprof 7272 (talk) 03:33, 15 July 2014 (UTC)

Sentence and reference from Isolation section moved here

…until I can discern if the material is of real continuing value to the article. Here is the stray sentence I could not place:

"A problem vis-a-vis the utility of isolation and purification to supply practical needs is that isolates often work differently than the original natural products which have synergies and may combine, say, antimicrobial compounds with compounds that stimulate various pathways of the immune system."

Left here until the source can be checked, and its value assessed, and a place found for it. Le Prof Leprof 7272 (talk) 09:17, 15 July 2014 (UTC)

Current article outline

Here is the current outline under discussion by editors active at this article: natural product outline. PLease join in the comments and discussion! (All discussion about the outline should be at this Talk page, and not at the Talk page associated with the link.) Cheers. Le Prof Leprof 7272 (talk) 00:29, 15 July 2014 (UTC)

Revised outline deleted by Boghog. I have no idea where we are now supposed to turn for a complete, combined outline of the article, sans individual editor writings. I give up. I thought it was a good idea, but he is the boss here. Le Prof Leprof 7272 (talk) 05:00, 15 July 2014 (UTC)

@Leprof 7272: What is the problem with including individual editor writings? Sometimes outlines become overly abstract and in these situations it helps to flesh out the outline to determine if the outline is workable. Furthermore for the reasons stated here, working on the outline in a subdirectory has distinct advantages. We can discuss the outline here and but keep the outline itself here. Boghog (talk) 05:50, 15 July 2014 (UTC)

Already answered below. Your sandbox is your sandbox. A commonly, mutually developed and controlled outline is just that. No more responses here. Le Prof Leprof 7272 (talk) 06:19, 15 July 2014 (UTC)

@Leprof 7272: My sandbox is here. You and anyone else are welcome to make changes to this article's outline sandbox here. Boghog (talk) 06:24, 15 July 2014 (UTC)

Take the point: I/we will not join you. Your adding your text content to the outline without discussion, and as sole party doing so, makes this link of yours also your sandbox. I will not contribute to anything that does not remain a simple bare, decimal type outline where all persons are on equal footing contributing. The point of the outline is to limit and focus discussion. Adding text defies this end. If necessary I will develop a common outline somewhere, if one does not re-appear very soon (though this will signal departure from collaborative work). Enjoy your added sole work venue if you choose. I have nothing more to say. Le Prof Leprof 7272 (talk) 06:36, 15 July 2014 (UTC)

@Leprof 7272: Revised outline deleted by Boghog. – False. I have collapsed it, not deleted it. Furthermore:

• You added a number of comments to your outline. I did not complain. When I added some draft text, you complained. That is hypocrisy.
• I then collapsed the draft text. You still complained. That is unreasonable.
• You then demanded a bare, decimal type outline. That is bizarre. There is absolutely no difference in the mechanics of editing the outline page as opposed to the talk page or to a Wikipedia article. You, I, and other editors are already familiar with section heading syntax. The advantage of using this syntax is that is makes it much easier to navigate and edit. If one changes the order or inserts or deletes sections, the sections are automatically renumbered. Why not take advantage of MediaWiki markup language that was designed to solve exactly this type of problem?
• You then claimed that an outline minus comments is the only way where all persons are on equal footing contributing. That is bullshit. Just as everyone is free to edit this article, everyone is also free to edit the draft outline and therefore everyone is on an equal footing.
• You then insisted that the only collaborative way forward is to work on a outline that is free of comments or draft text. That is arrogant.
• Why should I or anyone else follow your made up rules? Boghog (talk) 17:23, 15 July 2014 (UTC)

Proposed content for revised classes section

The following is suggested by User:Boghog, as further text for the classes section. Moved here so we all can use and revise the outline as an outline (leaving text generation for later, for everyone, in their sandboxes or in the article).

Extended content

HEADING Classes == SUBHEADNG Based on function === Following Albrecht Kossel's original proposal in 1891, natural products are often divided into two major classes, the primary and secondary metabolites. Primary metabolites have an intrinsic function that is essential to the survival of the organism that produces them. Secondary metabolites in contrast have an extrinsic function that mainly affects other organisms. Secondary metabolites are not essential to survival but do increase the competitiveness of the organism within its environment. SUBSUBHEADNG Primary metabolites ==== Primary metabolites as defined by Kossel are components of basic metabolic pathways that are required for life. They are associated with essential cellular functions such as nutrient assimilation, energy production, and growth/development. They have a wide species distribution that span many phyla and frequently more than one kingdom. Primary metabolites include carbohydrates, lipids, amino acids, and nucleic acids which are the basic building blocks of life. Primary metabolites that are involved with energy production include respiratory and photosynthetic enzymes. Enzymes in turn are composed of amino acids and often non-peptidic cofactors that are essential for enzyme function. The basic structure of cells and of organisms are also composed of primary metabolites. These include cell membranes (phospholipids), cell walls (peptidoglycans), and cytoskeletons (proteins). DNA and RNA which store and transmit genetic information are composed of nucleic acid primary metabolites. First messengers are signaling molecules that control metabolism or cellular differentiation. These signaling molecules include hormones and growth factors in turn are composed of peptides, biogenic amines, steroid hormones, auxins, gibberellins, etc. These first messengers interact with cellular receptors which are composed of proteins. Cellular receptor in turn activate second messengers are used to relay the extracellular message to intracellular targets. These signaling molecules include the primary metabolites cyclic nucleotides, diacyl glycerol, etc. SUBSUBHEADNG Secondary metabolites ==== Secondary in contrast to primary metabolites are dispensable and are not absolutely required for survival. Furthermore secondary metabolites typically have a narrow species distribution. Other than they are dispensable, the function of many secondary metabolites is otherwise unknown. It is assumed however that they confer a competitive advantage to the organism that produces them. An alternative view is that in analogy to the immune system, a majority of individual secondary metabolites have no specific function, but having the machinery in place to produce these diverse chemical structures is important so that a few useful secondary metabolites that are useful are produced and selected for. Secondary metabolites are used for a broad range of purposes. These include pheromones that act as social signaling molecules with other individuals of the same species, signaling molecules that attract and activate symbiotic organisms, agents that solubilize and transport nutrients (siderophores, etc.), and competitive weapons (repellants, venoms, toxins, etc.) that are used against competitors, prey, and predators. General structural classes of secondary metabolites include alkaloids, phenylpropanoids, polyketides, and terpenoids which are described in more detail in the biosynthesis section below. }} Le Prof Leprof 7272 (talk) 00:41, 15 July 2014 (UTC) This was the only other text addition that appeared in the outline, and it is also placed here, so it will not be lost, and time wasted. The biosynthetic pathways leading to the major classes of natural products are described below. Le Prof Leprof 7272 (talk) 01:37, 15 July 2014 (UTC) References

The discussion should take place here, but the outline in the Talk:Natural_product/Outline subdirectory is much more legible. Comments here are certainly welcome, but I will continue to work on expanding the version in the talk page subdirectory. Boghog (talk) 05:07, 15 July 2014 (UTC)

The link provided immediately above is to a sandbox of Boghog's and not to an agreed upon general, all-editor outline under discussion. Here is the nearest link to an outline, Talk:Natural_product#Proposed_article_outline, though it does not have Boghog's later ideas and material incorporated. It is up to him to create such a general outline, leaving his writings in his sandbox, and leaving the outline an outline, at whatever general location he wishes. My effort to generate an up to date outline was deleted, and I am not going to the effort to recreate it. And I am not editing in another's sandbox. Le Prof Leprof 7272 (talk) 06:18, 15 July 2014 (UTC)

@Leprof 7272: The Talk:Natural_product/Outline subdirectory is not my sandbox, it is the article's sandbox and anyone is free to edit it. Boghog (talk) 06:27, 15 July 2014 (UTC)

Take the point: I/we will not join you. Your adding your text content to the outline without discussion, and as sole party doing so, makes this link of yours also your sandbox. I will not contribute to anything that does not remain a simple bare, decimal type outline where all persons are on equal footing contributing. The point of the outline is to limit and focus discussion. Adding text defies this end. If necessary I will develop a common outline somewhere, if one does not re-appear very soon (though this will signal departure from collaborative work). Enjoy your added sole work venue if you choose. I have nothing more to say. Le Prof Leprof 7272 (talk) 06:36, 15 July 2014 (UTC)

@Leprof 7272: "I/we" – speak for yourself. As I have stated on my talk page, sometimes outlines become overly abstract and in these situations it helps to flesh out the outline to determine if the outline is workable. That was my intention. Furthermore having an outline on a talk page is awkward since you are asking people to refactor your comments. It is much cleaner to move it to a subdirectory. Finally there is a "bare, decimal type outline" at the top of the Talk:Natural product/Outline page that is labeled "Contents". Boghog (talk) 07:02, 15 July 2014 (UTC)

quam subterfugium. Change of location long granted, as you well know. To repeat what I have already said, essentially, at your Talk page: The autogenerated TOC at top of page does not fulfill my requirement for a directly edited simple outline where all are on equal editorial footing (because sub-points of the outline disappearing into text disappear form the outline, etc.). I am not going to argue this further. Dead end alternative; unacceptable. The only way forward I see is this: Feel free to delete all explanatory comments carried over from my earlier draft outline that you seem to imply offend or give justification to your amalgam; do what you need to do to make the outline fulfill your perception of a simple bare, decimal type outline that all users can add to or edit. Please, then, by doing this and removing your text, and posting the outline somewhere, let me know that you are willing to work together. Or, tell me you will not do so. (As simple as that; "I will not do so.") I will not comment further, again, unless the decision is to work together. Report the location of the simple outline you create (or report that you are not willing to work with me), here. Otherwise, this is all from me; I am done. Le Prof Leprof 7272 (talk) 07:25, 15 July 2014 (UTC)

OK, good. We agree that the location of the outline can be moved. As a compromise, I have collapsed the draft prose in the Talk:Natural_product/Outline. Is this acceptable? Boghog (talk) 07:44, 15 July 2014 (UTC)

quam subterfugium. You are not compromising, you are maintaining your position. Nonstarter. Le Prof Leprof 7272 (talk) 08:20, 15 July 2014 (UTC)

There are a whole lot of missunderstandings above and on my talk page that need to be corrected.

• Once again, with sweep of hand you set aside an hour of work without regard. – the only thing that I did to your work was collapse it. It is still found above. What you did to my work was to fragment it into an incomprehensible mess.
• Feel free to delete all explanatory comments carried over from my earlier draft outline that you seem to imply offend or give justification to your amalgam – I was only pointing out that the draft prose was equivalent to a comment. Why can't we leave both the comments and the draft text in place? This is more much more efficient.
• The autogenerated TOC at top of page does not fulfill my requirement for a directly edited simple outline where all are on equal editorial footing (because sub-points of the outline disappearing into text disappear form the outline, etc.). – Huh? If you want something to appear in the outline, simply create a new subheading. Furthermore it is obvious that everyone is has an equal editorial footing since anyone is free to edit any part of the subdirectory. You have not explained why the draft outline is unacceptable. The arguments that you have offered simply do not add up.
• At several points, you refer to other editors. I also hope that other editors will join this discussion. However by my count, you have scared off at least three other editors. The fact of the matter is that there are only two editor actively working on this article. You and me. We need to work together.
• And finally why should [your] requirements be the final word? In other words, why should I play by your made up rules? Boghog (talk) 14:05, 15 July 2014 (UTC)

PS: There is an older version of the outline that doesn't have any prose.

PPS: As mentioned above, there are still two outstanding questions: The composition of the function section and whether or not we should merge the biosynthesis and structure sections. An indication of whether these two specific proposals are acceptable or not would be appreciated. Boghog (talk) 14:47, 15 July 2014 (UTC)

Consolidated response to bifurcated misinformation

Here are your two sets of responses, @User:Boghog:

Extended content

There are a whole lot of missunderstandings above and on my talk page that need to be corrected. Once again, with sweep of hand you set aside an hour of work without regard. – the only thing that I did to your work was collapse it. It is still found above. What you did to my work was to fragment it into an incomprehensible mess. Feel free to delete all explanatory comments carried over from my earlier draft outline that you seem to imply offend or give justification to your amalgam – I was only pointing out that the draft prose was equivalent to a comment. Why can't we leave both the comments and the draft text in place? This is more much more efficient. The autogenerated TOC at top of page does not fulfill my requirement for a directly edited simple outline where all are on equal editorial footing (because sub-points of the outline disappearing into text disappear form the outline, etc.). – Huh? If you want something to appear in the outline, simply create a new subheading. Furthermore it is obvious that everyone is has an equal editorial footing since anyone is free to edit any part of the subdirectory. You have not explained why the draft outline is unacceptable. The arguments that you have offered simply do not add up. At several points, you refer to other editors. I also hope that other editors will join this discussion. However by my count, you have scared off at least three other editors. The fact of the matter is that there are only two editor actively working on this article. You and me. We need to work together. And finally why should [your] requirements be the final word? In other words, why should I play by your made up rules? Boghog (talk) 14:05, 15 July 2014 (UTC) PS: There is an older version of the outline that doesn't have any prose. PPS: As mentioned above, there are still two outstanding questions: The composition of the function section and whether or not we should merge the biosynthesis and structure sections. An indication of whether these two specific proposals are acceptable or not would be appreciated. Boghog (talk) 14:47, 15 July 2014 (UTC) }} and @Leprof 7272: Revised outline deleted by Boghog. – False. I have collapsed it, not deleted it. Furthermore: You added a number of comments to your outline. I did not complain. When I added some draft text, you complained. That is hypocrisy. I then collapsed the draft text. You still complained. That is unreasonable. You then demanded a bare, decimal type outline. That is bizarre. There is absolutely no difference in the mechanics of editing the outline page as opposed to the talk page or to a Wikipedia article. You, I, and other editors are already familiar with section heading syntax. The advantage of using this syntax is that is makes it much easier to navigate and edit. If one changes the order or inserts or deletes sections, the sections are automatically renumbered. Why not take advantage of MediaWiki markup language that was designed to solve exactly this type of problem? You then claimed that an outline minus comments is the only way where all persons are on equal footing contributing. That is bullshit. Just as everyone is free to edit this article, everyone is also free to edit the draft outline and therefore everyone is on an equal footing. You then insisted that the only collaborative way forward is to work on a outline that is free of comments or draft text. That is arrogant. Why should I or anyone else follow your made up rules? Boghog (talk) 17:23, 15 July 2014 (UTC) }}

and my final response:

You are wasting time in multiple venues at the same page, and at multiple pages, and I'm done with it. I have stated what I need to be able to work with you, and I will state it again at the close. For the last time. in combined response to this amazing set of bullets: (1) Move of outline. Stated repeatedly, relocation of the outline (its editing outside of Talk) is fine by me. Full stop, off the table. Now, we just need an agreed upon outline to start from. (2) Mess made of outline. Inadvertent, reversible, beside the point: (a) moved your text here to Talk, so conveniently availalble, and (b) returned the outline to being a simple outline, by reducing added text to outline form. (3) Alternative to reverting. If the "messy" form of the derived outline was unacceptable, it could have been over-pasted with a better form of your revised outline, or tidied up via editing. Instead you reverted en masse, so it is true that you swept away my work. Period, see next. (4) Late offer to collapse. Your proposal to collapse your text sections only came much later, so it is completely disingenuous to convolute the timeline, muddying the fact that I was reverted en masse early, confounding this with your collapse markup (which came late). Regardless, collapsing is not an acceptable variant; it solves none of the inherent problems of the amalgam. (5) My comments added. (a) you never before objected to the brief, sporadic, explanatory comments appearing in the first draft outline, (b) they were put in to make clear the meanings of the bullet points, and (c) you were given leave to remove them. It is again completely disingenuous of you to suggest these brief comments are equivalent to your beginning to convert part of the outline to final text. This is further subterfugio, and beneath both of us. (6) TOC as outline unacceptable. To repeat, yet again: The auto-generated TOC is an unacceptable alternative to a real, editable outline because as you compose, converting outline bullets to text, the outline changes, with parts unacceptably disappearing from the TOC. This and other reasons more subtle make the auto-generated TOC of your amalgam unacceptable to me as the shared, working outline. (7) My demanding final word. A further red herring / further subterfugio. Your reversion of my edit and obstinance to retain the reversion is just as much a demand to have final word. mdr (8) Interested/scared editors, etc. I have neither your clairvoyance about past nor prophetic skill regarding future, so no comment. (9) Re: hypocrisy, bullshit, arrogant. You are entitled to your opinions; but keep in mind having expressed them when you correct others about their conduct here.

I close with slightly emphasized re-statements of things already said: I have been requesting a joint outline since 20 June (see [22]): We need an outline document that is mutually owned, with no greater ownership/control by one or another editor. An amalgamated document defeats this purpose. An amalgam of single user-generated text plus outline convolutes the stages of outline discussion and subsequent composition, imbalances ownership of the document toward anyone having desire and time to convert outline to text (which will be to you, as it is just us, and I will not participate), it dilutes the information under discussion (making it necessary to derive bullet points from prose where text has replaced bullets), and as one composes, the subsection bullets of the outline also disappear from the auto-derived TOC (making this feature useless as a replacement for the requested outline). Bottom line, for 50% of this collaboration, your un-discussed, and as such, imposed alternative format of composition-amalgamated-with-outline, differing from that originally offered ([23]), while fine for your personal use and sandbox, is not a workable, common, simple outline document suitable for relaxed discussion with me.

So there are two options, offered again in closing, because I will not rehash the foregoing another time. Please, choose one:

• Update the outline, as an outline, no composition, creating a new working outline that we both can review and discuss (eliminating explanatory comments that offend you), or
• Choose not to, and call an end to further discussion over this and any matter regarding the longer term direction of the article.

In the spirit of Wikipedia, I hope you choose the former. On a personal level, this last round with you leaves me near hopeless regarding either. Le Prof Leprof 7272 (talk) 05:11, 16 July 2014 (UTC)

I have carefully read your response, but I still honestly don't understand your objections to the draft outline. It is completely irrelevant when offers were made. The only thing that matters is the offers that are currently on the table. Regardless, as mentioned above, there are still two outstanding questions: The composition of the function section and whether or not we should merge the biosynthesis and structure sections. An indication of whether these two specific proposals are acceptable or not would be appreciated. Boghog (talk) 06:16, 16 July 2014 (UTC)

Further arguments as to the proper format of an outline are pointless. I believe the most convenient format uses MediaWiki section heading syntax. You don't. You also apparently are unwilling to discuss the draft outline unless it is reformatted. I think reformatting this outline would be a step backwards. Hence I have inserted the classes section of the outline along with the proposed text directly into the article. We can view the additions in the article and discuss them here. Boghog (talk) 13:16, 16 July 2014 (UTC)

@Leprof 7272: I have restored your bullet points and retained the collapsed draft prose in the draft outline. Please note that I never objected to having notes in the outline. Quite to the contrary, I think it is much more efficient to retain both the notes and the draft prose in one place rather than splitting them between the outline and talk page. Furthermore the draft prose is collapsed. If you don't want to look at it, ignore it. Boghog (talk) 06:19, 21 July 2014 (UTC)

I have looked back to this article periodically, and seen no real progress. whatsoever, in its content. If I return to begin work on this article, per the earlier outline, will you, Boghog, suddenly find it a priority to return to this article (despite no edits since July), and re-exert your control over its evolution? I have left it to you for 4 mos. May I have leave (of you, I have no other concerns for editors here) to work on this article now? Le Prof Leprof 7272 (talk) 12:23, 27 November 2014 (UTC)

@Leprof 7272: Thank you for inserting section headings in your new outline. It now becomes much clearer. However there was already a perfectly good outline here that is a subdirectory of this talk page. Why is necessary to create yet another outline? Unless of course you want to reclaim your controlling influence over its evolution. To assert that a subdirectory of this article talk page is my private sandbox is absurd. This outline is no more my sandbox than this article's archives. Finally I remind you of WP:NORUSH. I work in spurts. I may heavily edit an article for a few days, and then return to it a few years later. Boghog (talk) 19:19, 1 December 2014 (UTC)

While adding section headings is an improvement, it makes a mess of this talk page table of contents. Furthermore this page talk is also automatically archived by section headings which will eventually scramble the order of this outline. I have therefore move it to its own subdirectory here: Talk:Natural product/Outline2. (Please note that is a talk page subdirectory, NOT a sandbox.) Boghog (talk) 06:11, 2 December 2014 (UTC)

Working outline for development of article

The following is a working outline of the article, contributed by two interested editors. Please feel free to offer edits to this outline, esp. starting with highest level of outline points (charting the broad course of the article), and to add discussion of your additions below the outline.

Note, the purpose of THIS version of the outline is not to become a place for text elaboration of ideas—apart from simple one-liners, to make clear what is proposed by a new or changed outline section or subsection. If anything more than outline bullets are desired, editor Boghog has created and linked to more of a sandbox-type of outline, that can be accessed above.

Finally, not all content is necessarily agreed upon that appears here. The outline is a work in progress, and is intended to reflect the eventual consensus of those participating (where the discussion that follows should be used to judge the extent of current consensus).

Talk:Natural product/Outline2

Cheers, look forward to input. Le Prof Leprof 7272 (talk) 13:31, 27 November 2014 (UTC)

There is a pre-existing outline here. Let us keep the discussion in one place. I look forward to your input there. Cheers. Boghog (talk) 19:23, 1 December 2014 (UTC)

On second thought, why don't we dispense with these outlines entirely? The Classes (now divided into Function, Biosynthesis, and Sources) and Medical uses sections of the live version of the article are more or less consistent with both outlines. The rest of the sections I am much less concerned about and you are free to edit as you see fit. Agreed? Boghog (talk) 21:02, 1 December 2014 (UTC)

Contributions of natural products to drug discovery

@Zefr: Thanks for adding the Li et al. 2009 citation. However as Li makes clear, I think you overstated the limitations of natural products as the source of new drugs. In particular, Li states:

• Li JW, Vederas JC (July 2009). "Drug discovery and natural products: end of an era or an endless frontier?". Science. 325 (5937): 161–5. doi:10.1126/science.1168243. PMID 19589993. With the current framework of HTS in major pharmaceutical industries and increasing government restrictions on drug approvals, it is possible that the number of new natural product–derived drugs could go to zero. However, this is likely to be temporary, as the potential for new discoveries in the longer term is enormous.

Other more recent sources emphasize that natural product drug discovery is still making important contributions:

• Harvey AL, Edrada-Ebel R, Quinn RJ (2015). "The re-emergence of natural products for drug discovery in the genomics era". Nature Reviews. Drug Discovery. 14 (2): 111–29. doi:10.1038/nrd4510. PMID 25614221. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced [technical barriers to screening natural products in high-throughput assays]. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.
• Newman DJ, Cragg GM (2016). "Natural Products as Sources of New Drugs from 1981 to 2014". Journal of Natural Products. 79 (3): 629–61. doi:10.1021/acs.jnatprod.5b01055. PMID 26852623. ... the utilization of natural products and/or their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over the time frame from around the 1940s to the end of 2014, of the 175 small molecules approved, 131, or 75%, are other than "S" (synthetic), with 85, or 49%, actually being either natural products or directly derived therefrom.
• Torre BG, Albericio F (2017). "The Pharmaceutical Industry in 2016. An Analysis of FDA Drug Approvals from a Perspective of the Molecule Type". Molecules (Basel, Switzerland). 22 (3). doi:10.3390/molecules22030368. PMID 28264468. The outputs from 2016 indicate the so-called small molecules are losing ground against biologics, biomolecules, and other molecules inspired [by] natural products{{cite journal}}: CS1 maint: unflagged free DOI (link)

It is true that natural product drug discovery has declined from its peak, but HTS of synthetic compound libraries also has its drawbacks and the decline in productivity in the pharmaceutical industry has been blamed in part on the over reliance on synthetic compound screening. Consequently natural product drug discovery has been staging somewhat of a comeback. Boghog (talk) 18:55, 30 April 2017 (UTC)

Boghog: I agree with your assessment which indicates need for your further editing to add balance. Before my edits, there was a dearth of overall discussion on the quantity of lead development between natural products and HTS. Filling this out further would benefit the article, but even the sources you cite above give the impression of tepid growth this decade in developing drugs from natural sources. The diversity of potential leads from bacterial and marine sources warrants more attention, imo, but this then falls into WP:CRYSTAL, so perhaps not. --Zefr (talk) 19:23, 30 April 2017 (UTC)