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John R. Falck

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John Russell "Camille" Falck (born December 2, 1948) is an American chemist, Professor of Biochemistry, and holder of the Robert A. Welch Distinguish Chair in Chemistry at the University of Texas Southwestern Medical Center (UT SW Medical Center).[1] In 1996 he was awarded the Wilfred T. Doherty Recognition Award from the Dallas-Fort Worth Section of the American Chemical Society [2] and a Recognition Award at the March 10, 2002, Winter Eicosanoid Conference (Baltimore MD) in appreciation of his significant contributions to the chemistry of natural products, and to the identification and functional characterization of the cytochrome P450 (P450) arachidonic acid (AA) monooxygenase metabolic pathway and its metabolites.[3]

Early life and career

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Falck was born in the then US territory of Alaska, married Elaine R. Fogel (died 9/2008), and has two sons Benjamin and Aaron. He earned a BSc and PhD in organic chemistry from Colorado State University in 1970 and 1973, and a Diploma of Imperial College (DIC), London, England. After postdoctoral studies with Nobel laurates Derek H. R. Barton (Imperial College, London) and Elias J. Corey (Harvard University, MA) he joined the faculty at the then University of Texas Health Science Center (now UT SW Medical Center) in 1979. Falck has authored more than 820 peer-reviewed publications and awarded 40 patents.

Scientific contributions

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P450 AA monooxygenases

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Following initial reports of AA metabolism by P450 enzymes, Falck completed the first structural characterization and synthesis of 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) and of 19- and 20-hydroxyeicosatetraenoic acids (19- and 20-HETEs), and characterized them as products of the epoxygenase and ω/ω-1 hydroxylase branches of the P450 AA Monooxygenase, respectively.[4][5] These synthetic achievements were followed by Falck's early contributions to the: a) development of analytical methods for the identification of EETs and 19- and 20-HETE as products of endogenous metabolism of AA by P450 enzymes,[6][7][8][9] b) establishment of the P450 AA Monooxgenase as a branch of the AA metabolic cascade,[3][4][8] and c) characterization of biological activities associated with many of the P450 metabolites.[3][4] These accomplishments, highlighted in independent reviews,[10][11][12][13] were followed by Falck's development of synthetic EET and 20-HETE functional analogs/antagonists, which were of critical importance during the subsequent characterization of physiological and pathophysiological roles for these enzymes and their metabolites.[14][15][16]

Total syntheses

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Falck is known for his application of efficient, eco-friendly chemical procedures and/or strategies during the synthesis of a wide range of drug candidates, several of which are currently undergoing clinical evaluation. He has also confirmed the structures of several bioactive compounds found in natural products, and of short-lived intracellular second messengers that mediated cellular responses to environmental stimuli.

Development of chemical and biochemical techniques and tools

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Falck's contributions range from practical methods for creating carbon-carbon,[17][18] carbon-nitrogen,[19][20][21] and carbon-oxygen [22] bonds to the visualization of acidic organelles inside cells.[23] He is also distinguished for developing the Falck-Bradsher annulation [24] used to prepare six-membered rings containing a nitrogen based upon a process chemists call an inverse electron demand [4+2]-cycloaddition.

References

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  1. ^ "J Falck, Ph.D. - Faculty Profile - UT Southwestern". profiles.utsouthwestern.edu.
  2. ^ Section, American Chemical Society Dallas/Fort Worth; Strom, E. Thomas (April 16, 1996). "Southwest Retort, Volume 49, Number 8, April 1996". Southwest Retort. 49 (8) – via digital.library.unt.edu.
  3. ^ a b c Capdevila, Jorge H.; Falck, John R. (1 November 2018). "Thematic Review Series: Living History of Lipids The arachidonic acid monooxygenase: from biochemical curiosity to physiological/pathophysiological significance". Journal of Lipid Research. 59 (11): 2047–2062. doi:10.1194/jlr.R087882. ISSN 0022-2275. PMC 6210905. PMID 30154230.
  4. ^ a b c Moustakis, Christine A.; Viala, Jacques; Capdevila, Jorge; Falck, J. R. (September 1985). "Total synthesis of the cytochrome P-450 epoxygenase metabolites 5(R),6(S)-, 5(S),6(R)-, and 14(R),15(S)-epoxyeicosatrienoic acid (EET) and hydration products 5(R),6(R)- and 14(R),15(R)-dihydroxyeicosatrienoic acid (DHET)". Journal of the American Chemical Society. 107 (18): 5283–5285. doi:10.1021/ja00304a048. ISSN 0002-7863.
  5. ^ Capdevila, JH; Falck, JR; Harris, RC (February 2000). "Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase". Journal of Lipid Research. 41 (2): 163–81. doi:10.1016/S0022-2275(20)32049-6. PMID 10681399.
  6. ^ Gopal, V. Raj; Jagadeesh, S. G.; Reddy, Y. Krishna; Bandyopadhyay, A.; Capdevila, Jorge H.; Falck, J. R. (15 March 2004). "A practical, stereospecific route to 18-, 19-, and 20-hydroxyeicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acids (18-, 19-, and 20-HETEs)". Tetrahedron Letters. 45 (12): 2563–2565. doi:10.1016/j.tetlet.2004.01.151. ISSN 0040-4039.
  7. ^ Capdevila, Jorge H.; Wei, Shouzou; Kumar, Anil; Kobayashi, Jun; Snapper, James R.; Zeldin, Darryl C.; Bhatt, Rama K.; Falck, John R. (1 December 1992). "Resolution of dihydroxyeicosanoates and of dihydroxyeicosatrienoates by chiral phase chromatography". Analytical Biochemistry. 207 (2): 236–240. doi:10.1016/0003-2697(92)90006-S. ISSN 0003-2697. PMID 1481976.
  8. ^ a b Karara, A; Dishman, E; Blair, I; Falck, JR; Capdevila, JH (25 November 1989). "Endogenous epoxyeicosatrienoic acids. Cytochrome P-450 controlled stereoselectivity of the hepatic arachidonic acid epoxygenase". The Journal of Biological Chemistry. 264 (33): 19822–7. doi:10.1016/S0021-9258(19)47185-8. PMID 2584196.
  9. ^ Zeldin, DC; Kobayashi, J; Falck, JR; Winder, BS; Hammock, BD; Snapper, JR; Capdevila, JH (25 March 1993). "Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase". The Journal of Biological Chemistry. 268 (9): 6402–7. doi:10.1016/S0021-9258(18)53266-X. PMID 8454612.
  10. ^ McGiff, John C.; Quilley, John (March 2001). "20-Hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids and blood pressure". Current Opinion in Nephrology and Hypertension. 10 (2): 231–237. doi:10.1097/00041552-200103000-00012. ISSN 1062-4821. PMID 11224699. S2CID 44774278.
  11. ^ Roman, RJ (January 2002). "P-450 metabolites of arachidonic acid in the control of cardiovascular function". Physiological Reviews. 82 (1): 131–85. doi:10.1152/physrev.00021.2001. PMID 11773611.
  12. ^ Pfister, Sandra L.; Gauthier, Kathryn M.; Campbell, William B. (1 January 2010). "Vascular Pharmacology of Epoxyeicosatrienoic Acids". Chapter 2 - Vascular Pharmacology of Epoxyeicosatrienoic Acids. Advances in Pharmacology. Vol. 60. Academic Press. pp. 27–59. doi:10.1016/b978-0-12-385061-4.00002-7. ISBN 978-0-12-385061-4. PMC 3373307. PMID 21081214.
  13. ^ Imig, John D. (1 July 2013). "Epoxyeicosatrienoic acids, 20-hydroxyeicosatetraenoic acid, and renal microvascular function". Prostaglandins & Other Lipid Mediators. 104–105: 2–7. doi:10.1016/j.prostaglandins.2013.01.002. ISSN 1098-8823. PMC 3664103. PMID 23333581.
  14. ^ Alonso-Galicia, Magdalena; Falck, John R.; Reddy, Komandla Malla; Roman, Richard J. (1 November 1999). "20-HETE agonists and antagonists in the renal circulation". American Journal of Physiology. Renal Physiology. 277 (5): F790–F796. doi:10.1152/ajprenal.1999.277.5.F790. ISSN 1931-857X. PMID 10564244.
  15. ^ Falck, JR; Koduru, SR; Mohapatra, S; Manne, R; Atcha, KR; Atcha, R; Manthati, VL; Capdevila, JH; Christian, S; Imig, JD; Campbell, WB (28 August 2014). "14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates: carboxylate modifications". Journal of Medicinal Chemistry. 57 (16): 6965–72. doi:10.1021/jm500262m. PMC 4148164. PMID 25119815.
  16. ^ Campbell, William B.; Imig, John D.; Schmitz, James M.; Falck, John R. (October 2017). "Orally Active Epoxyeicosatrienoic Acid Analogs". Journal of Cardiovascular Pharmacology. 70 (4): 211–224. doi:10.1097/FJC.0000000000000523. ISSN 0160-2446. PMC 5673125. PMID 28937442.
  17. ^ Falck, J. R.; Bhatt, Rama K.; Ye, Jianhua (June 1995). "Tin-Copper Transmetalation: Cross-Coupling of .alpha.-Heteroatom-Substituted Alkyltributylstannanes with Organohalides". Journal of the American Chemical Society. 117 (22): 5973–5982. doi:10.1021/ja00127a010. ISSN 0002-7863.
  18. ^ Ye, Jianhua; Bhatt, Rama K.; Falck, J. R. (10 December 1993). "Stereospecific α-alkoxystannane couplings with acyl chlorides: Total synthesis of (+)-goniofufurone". Tetrahedron Letters. 34 (50): 8007–8010. doi:10.1016/S0040-4039(00)61436-3. ISSN 0040-4039.
  19. ^ Jat, Jawahar L.; Paudyal, Mahesh P.; Gao, Hongyin; Xu, Qing-Long; Yousufuddin, Muhammed; Devarajan, Deepa; Ess, Daniel H.; Kürti, László; Falck, John R. (3 January 2014). "Direct Stereospecific Synthesis of Unprotected N-H and N-Me Aziridines from Olefins". Science. 343 (6166): 61–65. Bibcode:2014Sci...343...61J. doi:10.1126/science.1245727. ISSN 0036-8075. PMC 4175444. PMID 24385626.
  20. ^ Paudyal, Mahesh P.; Adebesin, Adeniyi Michael; Burt, Scott R.; Ess, Daniel H.; Ma, Zhiwei; Kürti, László; Falck, John R. (9 September 2016). "Dirhodium-catalyzed C-H arene amination using hydroxylamines". Science. 353 (6304): 1144–1147. Bibcode:2016Sci...353.1144P. doi:10.1126/science.aaf8713. ISSN 0036-8075. PMC 5040325. PMID 27609890.
  21. ^ Anugu, Raghunath Reddy; Munnuri, Sailu; Falck, John R. (18 March 2020). "Picolinate-Directed Arene meta -C–H Amination via FeCl 3 Catalysis". Journal of the American Chemical Society. 142 (11): 5266–5271. doi:10.1021/jacs.9b13753. ISSN 0002-7863. PMID 32090542. S2CID 211262974.
  22. ^ Falck, J.R.; Yu, Jurong; Cho, Hyun-Sung (August 1994). "A convenient synthesis of unsymmetric polyfluoroethers". Tetrahedron Letters. 35 (33): 5997–6000. doi:10.1016/0040-4039(94)88058-1.
  23. ^ Anderson, R G; Falck, J R; Goldstein, J L; Brown, M S (August 1984). "Visualization of acidic organelles in intact cells by electron microscopy". Proceedings of the National Academy of Sciences. 81 (15): 4838–4842. Bibcode:1984PNAS...81.4838A. doi:10.1073/pnas.81.15.4838. ISSN 0027-8424. PMC 391586. PMID 6146980.
  24. ^ Bolitt, Veronique; Mioskowski, Charles; Kollah, R. Ominde; Manna, Sukumar; Rajapaksa, D.; Falck, J. R. (July 1991). "Total synthesis of vineomycinone B2 methyl ester via double Bradsher cyclization". Journal of the American Chemical Society. 113 (16): 6320–6321. doi:10.1021/ja00016a086. ISSN 0002-7863.
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