Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus.
Aflastatin A (1) is a specific inhibitor of aflatoxin production by Aspergillus parasiticus. It has the novel structure of a tetramic acid derivative with a long alkyl side chain. The absolute configurations of 29 chiral centers contained in 1 were chemically elucidated in this study. First, four small fragment molecules were prepared from 1 or its methyl ether (2), and their absolute structures were assigned as N-methyl-D-alanine, (2S,4R)-2, 4-dimethyl-1,6-hexanediol dibenzoate, (R)-3-hydroxydodecanoic acid, and (R)-1,2,4-butanetriol tribenzoate. Next, an acyclic fragment molecule 3 with 13 chiral centers was obtained from 1 by NaIO(4) oxidation, and its relative stereochemistry was elucidated by J-based configuration analysis. By analyzing coupling constants of (3)J(H,H) and (2,3)J(C,H) and ROE data, the relative configuration of 3 was verified. Finally, by further J-based configuration analysis using a fragment molecule 7 prepared from 2 with 28 chiral carbons, all relative configurations in the alkyl side chain of 1 were clarified. By connecting these relative configurations with the absolute configurations of first four fragment molecules, the absolute stereochemistry of 1 was fully determined.
Ikeda
H
H
Department of Applied Biological Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Matsumori
N
N
Ono
M
M
Suzuki
A
A
Isogai
A
A
Nagasawa
H
H
Sakuda
S
S
D000348:Aflatoxins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001230:Aspergillus / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D011760:Pyrrolidinones; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000348:Aflatoxins; D000900:Anti-Bacterial Agents; D011760:Pyrrolidinones; C105377:aflastatin A