Mollemycin A: an antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244)

Raju, Ritesh, Khalil, Zeinab G., Piggott, Andrew M., Blumenthal, Antje, Gardiner, Donald L., Skinner-Adams, Tina S. and Capon, Robert J. (2014) Mollemycin A: an antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244). Organic Letters, 16 6: 1716-1719. doi:10.1021/ol5003913


Author Raju, Ritesh
Khalil, Zeinab G.
Piggott, Andrew M.
Blumenthal, Antje
Gardiner, Donald L.
Skinner-Adams, Tina S.
Capon, Robert J.
Title Mollemycin A: an antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244)
Formatted title
Mollemycin A: an antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244)
Journal name Organic Letters   Check publisher's open access policy
ISSN 1523-7060
1523-7052
Publication date 2014-03-21
Year available 2017
Sub-type Article (original research)
DOI 10.1021/ol5003913
Open Access Status Not Open Access
Volume 16
Issue 6
Start page 1716
End page 1719
Total pages 4
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 1605 Organic Chemistry
Abstract Chemical analysis of an Australian coastal marine sediment-derived fungus, Phomopsis sp. (CMB-M0042F), yielded the known cytochalasins J (1) and H (2), together with five new analogues, cytochalasins J1-J3 (3-5) and H1 and H2 (6 and 7). Structures of 1-7 were assigned on the basis of detailed spectroscopic analysis, chemical interconversion, and biosynthetic and mechanistic considerations. Of note, 1 and 2 proved to be highly sensitive to acid-mediated transformation, with 1 affording 3-5 and 2 affording 6 and 7. Whereas 1, 2, 4, and 5 were detected as natural products in crude culture extracts, 3, 6, and 7 were designated as acid-mediated handling artifacts. We propose novel stereo- and regiospecific intramolecular cycloadditions, under tight functional group control, that facilitate selective conversion of 1 and 2 to the rare 5/6/6/7/5- and 5/6/5/8-fused heterocycles 5 and 7, respectively. Knowledge of acid sensitivity within the cytochalasin family provides a valuable cautionary lesson that has the potential to inform our analysis of past and future investigations into this structure class and inspire novel biomimetic transformations leading to new chemical diversity.
Formatted abstract
A marine-derived Streptomyces sp. (CMB-M0244) isolated from a sediment collected off South Molle Island, Queensland, produced mollemycin A (1) as a new first in class glyco-hexadepsipeptide-polyketide. The structure of 1 was assigned by detailed spectroscopic analysis, supported by chemical derivatization and degradation, and C3 Marfey’s analysis. Mollemycin A (1) exhibits exceptionally potent and selective growth inhibitory activity against Gram-positive and Gram-negative bacteria (IC50 10–50 nM) and drug-sensitive (3D7; IC50 7 nM) and multidrug-resistant (Dd2; IC50 9 nM) clones of the malaria parasite Plasmodium falciparum.
Keyword Organic Chemistry
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP120100183

Institutional Status UQ

 
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Created: Thu, 10 Apr 2014, 20:23:59 EST by Susan Allen on behalf of Institute for Molecular Bioscience