Sanglifehrin

Sanglifehrin A
Names
	Systematic IUPAC name (3S,6S,9R,10R,11S,12S,13E,15E,18S,21S)-18-{(2E,4E,8S,9S)-10-[(2S,3R,4S,5S,6R,9S,11S)-9-Ethyl-4-hydroxy-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undec-2-yl]-9-hydroxy-8-methyl-2,4-decadien-2-yl}-10, 12-dihydroxy-3-(3-hydroxybenzyl)-6-isopropyl-11-methyl-9-(3-oxobutyl)-19-oxa-1,4,7,25-tetraazabicyclo[19.3.1]pentacosa-13,15-diene-2,5,8,20-tetrone
Identifiers
CAS Number	187148-13-6 ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL410807 ;
ChemSpider	21395338 ;
DrugBank	DB03393;
PubChem CID	5388925;
CompTox Dashboard (EPA)	DTXSID101022539 ;
	InChI InChI=1S/C33H55NO8/c1-10-11-12-20(4)31(42-33(34)40)24(8)29(37)22(6)16-18(2)15-21(5)28(36)19(3)13-14-26(35)17-27-23(7)30(38)25(9)32(39)41-27/h10-15,19-31,35-38H,1,16-17H2,2-9H3,(H2,34,40)/b12-11-,14-13-,18-15-/t19-,20-,21-,22-,23-,24-,25+,26+,27-,28-,29+,30-,31-/m0/s1 ; InChI=1S/C60H91N5O13/c1-11-43-30-37(6)60(63-55(43)72)41(10)53(70)40(9)51(78-60)33-49(69)35(4)20-14-12-15-21-36(5)50-26-17-13-16-25-48(68)39(8)54(71)45(28-27-38(7)66)56(73)62-52(34(2)3)57(74)61-47(32-42-22-18-23-44(67)31-42)58(75)65-29-19-24-46(64-65)59(76)77-50/h12-13,15-18,21-23,25,31,34-35,37,39-41,43,45-54,64,67-71H,11,14,19-20,24,26-30,32-33H2,1-10H3,(H,61,74)(H,62,73)(H,63,72)/b15-12+,17-13+,25-16+,36-21+/t35-,37-,39-,40-,41-,43-,45+,46-,47-,48-,49-,50-,51-,52-,53-,54+,60+/m0/s1 Key: ONJZYZYZIKTIEG-CFBQITSMSA-N;
	SMILES CCC1CC(C2(C(C(C(C(O2)CC(C(C)CCC=CC=C(C)C3CC=CC=CC(C(C(C(C(=O)NC(C(=O)NC(C(=O)N4CCCC(N4)C(=O)O3)CC5=CC(=CC=C5)O)C(C)C)CCC(=O)C)O)C)O)O)C)O)C)NC1=O)C;
Properties
Chemical formula	C60H91N5O13
Molar mass	1090.4 g/mol
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Sanglifehrin A is a polyketide natural product found to potently inhibit cyclophilins and have immunosuppressive activity.^[1]

History

Isolation and characterisation of Sanglifehrins, produced by fermentation of Streptomyces sp. A92-308110 was first published by JJ Sanglier and T Fehr in 1999.^[2]

Structure

Sanglifehrins are mixed polyketide / non-ribosomal peptides, and their biosynthesis requires a modular type I polyketide synthase, with one module of non-ribosomal peptide synthetase, which incorporates phenylalanine, later converted by a hydroxylase to meta-tyrosine.^[3]

References

^ Zenke, G.; Strittmatter, U.; Fuchs, S.; Quesniaux, V. F.; Brinkmann, V.; Schuler, W.; Zurini, M.; Enz, A.; Billich, A.; Sanglier, J. J.; Fehr, T. (2001). "Sanglifehrin A, a novel cyclophilin-binding compound showing immunosuppressive activity with a new mechanism of action". Journal of Immunology. 166 (12): 7165–7171. doi:10.4049/jimmunol.166.12.7165. PMID 11390463. S2CID 11946118.
^ Sanglier, J. J.; Quesniaux, V.; Fehr, T.; Hofmann, H.; Mahnke, M.; Memmert, K.; Schuler, W.; Zenke, G.; Gschwind, L.; Maurer, C.; Schilling, W. (1999). "Sanglifehrins A, B, C and D, novel cyclophilin-binding compounds isolated from Streptomyces sp. A92-308110. I. Taxonomy, fermentation, isolation and biological activity". The Journal of Antibiotics. 52 (5): 466–473. doi:10.7164/antibiotics.52.466. PMID 10480570.
^ Qu, X.; Jiang, N.; Xu, F.; Shao, L.; Tang, G.; Wilkinson, B.; Liu, W. (2011). "Cloning, sequencing and characterization of the biosynthetic gene cluster of sanglifehrin A, a potent cyclophilin inhibitor". Molecular BioSystems. 7 (3): 852–861. doi:10.1039/c0mb00234h. PMID 21416665.

[1] Zenke, G.; Strittmatter, U.; Fuchs, S.; Quesniaux, V. F.; Brinkmann, V.; Schuler, W.; Zurini, M.; Enz, A.; Billich, A.; Sanglier, J. J.; Fehr, T. (2001). "Sanglifehrin A, a novel cyclophilin-binding compound showing immunosuppressive activity with a new mechanism of action". Journal of Immunology. 166 (12): 7165–7171. doi:10.4049/jimmunol.166.12.7165. PMID 11390463. S2CID 11946118.

[2] Sanglier, J. J.; Quesniaux, V.; Fehr, T.; Hofmann, H.; Mahnke, M.; Memmert, K.; Schuler, W.; Zenke, G.; Gschwind, L.; Maurer, C.; Schilling, W. (1999). "Sanglifehrins A, B, C and D, novel cyclophilin-binding compounds isolated from Streptomyces sp. A92-308110. I. Taxonomy, fermentation, isolation and biological activity". The Journal of Antibiotics. 52 (5): 466–473. doi:10.7164/antibiotics.52.466. PMID 10480570.

[3] Qu, X.; Jiang, N.; Xu, F.; Shao, L.; Tang, G.; Wilkinson, B.; Liu, W. (2011). "Cloning, sequencing and characterization of the biosynthetic gene cluster of sanglifehrin A, a potent cyclophilin inhibitor". Molecular BioSystems. 7 (3): 852–861. doi:10.1039/c0mb00234h. PMID 21416665.

[1]

[2]

[3]

History

Structure

See also

References