Viridicatumtoxin B

Viridicatumtoxin B
Names
	IUPAC name (1S,7a'S,11a'R)-5',6',7a',10',11a'-Pentahydroxy-3'-methoxy-2,6,6-trimethyl-7',8',12'-trioxo-7',7a',8',11',11a',12'-hexahydro-1'H-spiro[cyclohex-2-ene-1,2'-cyclopenta[de]tetracene]-9'-carboxamide
Identifiers
3D model (JSmol)	Interactive image; tautomer: Interactive image;
ChEBI	tautomer: CHEBI:218823;
ChemSpider	29355821; tautomer: 78441369;
PubChem CID	tautomer: 72204240;
	InChI InChI=1S/C30H29NO10/c1-11-6-5-7-27(2,3)28(11)9-12-16-18(13(32)8-15(41-4)21(16)28)22(34)20-17(12)23(35)29(39)10-14(33)19(26(31)38)24(36)30(29,40)25(20)37/h6,8,32-34,39-40H,5,7,9-10H2,1-4H3,(H2,31,38)/t28-,29-,30+/m0/s1 Key: SSOXEPGCLBSNOP-OIFRRMEBSA-N; tautomer: InChI=1S/C30H29NO10/c1-11-6-5-7-27(2,3)28(11)9-12-16-18(13(32)8-15(41-4)21(16)28)22(34)20-17(12)23(35)29(39)10-14(33)19(26(31)38)24(36)30(29,40)25(20)37/h6,8,32,34,36,39-40H,5,7,9-10H2,1-4H3,(H2,31,38)/t28-,29-,30+/m0/s1 Key: WUFPHUQCGWRGKE-OIFRRMEBSA-N;
	SMILES CC1=CCCC([C@@]12Cc3c4c2c(cc(c4c(c5c3C(=O)[C@]6(CC(=C(C(=O)[C@]6(C5=O)O)C(=O)N)O)O)O)O)OC)(C)C; tautomer: CC1=CCCC([C@@]12CC3=C4C2=C(C=C(C4=C(C5=C3C(=O)[C@]6(CC(=O)C(=C([C@]6(C5=O)O)O)C(=O)N)O)O)O)OC)(C)C;
Properties
Chemical formula	C30H29NO10
Molar mass	563.559 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Viridicatumtoxin B is a fungus-derived tetracycline-like antibiotic discovered in 2008. It was isolated from small amounts of penicillium fungi. A synthetic structure matching that of natural viridicatumtoxin B makes possible synthetic variants that match or surpass its antibiotic potency.^[1]

Analogs lacking a hydroxyl group were even more effective than the original against Gram-positive bacteria.^[1]

Concerns about solubility, biodegradation, availability and other issues must be resolved before clinical development begins.^[1]

History

The substance was first isolated from the mycelium of liquid fermentation cultures of Penicillium species FR11.^[2]

Structure

Based on mass spectrometry and nuclear magnetic resonance data, the substance was originally thought to be the 11a',12'-epoxide,^[2] but the structure was later revised.^[3]

Effects

Viridicatumtoxin B inhibited the growth of Staphylococcus aureus, including methicillin resistant S. aureus and quinolone-resistant S. aureus with a minimum inhibitory concentration of 0.5 μg/ml. That effect is similar to that of vancomycin, but 8 to 64 times greater than that of tetracycline.^[2]

Total synthesis

A complete total synthesis of viridicatumtoxin B, in racemic form, was completed in 2013 by the group of K. C. Nicolaou.^[3]^[4]

References

^ ^a ^b ^c "Synthesis produces new antibiotic". Research & Development. 28 August 2014. Retrieved 2015-10-09.
^ ^a ^b ^c Zheng, C. J.; Yu, H. E.; Kim, E. H.; Kim, W. G. (2008). "Viridicatumtoxin B, a new anti-MRSA agent from Penicillium sp. FR11". The Journal of Antibiotics. 61 (10): 633–7. doi:10.1038/ja.2008.84. PMID 19168978.
^ ^a ^b Nicolaou, K. C.; Hale, Christopher R. H.; Nilewski, Christian; Ioannidou, Heraklidia A.; Elmarrouni, Abdelatif; Nilewski, Lizanne G.; Beabout, Kathryn; Wang, Tim T.; Shamoo, Yousif (2014). "Total Synthesis of Viridicatumtoxin B and Analogues Thereof: Strategy Evolution, Structural Revision, and Biological Evaluation". Journal of the American Chemical Society. 136 (34): 12137–60. doi:10.1021/ja506472u. PMC 4210137. PMID 25317739.
^ Nicolaou, K. C.; Nilewski, Christian; Hale, Christopher R. H.; Ioannidou, Heraklidia A.; Elmarrouni, Abdelatif; Koch, Lizanne G. (2013). "Total Synthesis and Structural Revision of Viridicatumtoxin B". Angewandte Chemie International Edition. 52 (33): 8736–41. doi:10.1002/anie.201304691. PMC 3835450. PMID 23893651.

This systemic antibiotic-related article is a stub. You can help Wikipedia by expanding it.

[:0-1] "Synthesis produces new antibiotic". Research & Development. 28 August 2014. Retrieved 2015-10-09.

[doi84-2] Zheng, C. J.; Yu, H. E.; Kim, E. H.; Kim, W. G. (2008). "Viridicatumtoxin B, a new anti-MRSA agent from Penicillium sp. FR11". The Journal of Antibiotics. 61 (10): 633–7. doi:10.1038/ja.2008.84. PMID 19168978.

[Nicolau-3] Nicolaou, K. C.; Hale, Christopher R. H.; Nilewski, Christian; Ioannidou, Heraklidia A.; Elmarrouni, Abdelatif; Nilewski, Lizanne G.; Beabout, Kathryn; Wang, Tim T.; Shamoo, Yousif (2014). "Total Synthesis of Viridicatumtoxin B and Analogues Thereof: Strategy Evolution, Structural Revision, and Biological Evaluation". Journal of the American Chemical Society. 136 (34): 12137–60. doi:10.1021/ja506472u. PMC 4210137. PMID 25317739.

[4] Nicolaou, K. C.; Nilewski, Christian; Hale, Christopher R. H.; Ioannidou, Heraklidia A.; Elmarrouni, Abdelatif; Koch, Lizanne G. (2013). "Total Synthesis and Structural Revision of Viridicatumtoxin B". Angewandte Chemie International Edition. 52 (33): 8736–41. doi:10.1002/anie.201304691. PMC 3835450. PMID 23893651.

[1]

[2]

[3]

[4]