Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus

被引:45
作者
Ikeda, H
Matsumori, N
Ono, M
Suzuki, A
Isogai, A
Nagasawa, H
Sakuda, S [1 ]
机构
[1] Univ Tokyo, Dept Appl Biol Chem & Biotechnol, Bunkyo Ku, Tokyo 1138657, Japan
[2] Morinaga & Co Ltd, Inst Res, Tsurumi Ku, Yokohama, Kanagawa 2308504, Japan
[3] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 6300101, Japan
关键词
D O I
10.1021/jo991284c
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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 NaIO4 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.
引用
收藏
页码:438 / 444
页数:7
相关论文
共 27 条
[1]  
BERNARD CL, 1962, J AM CHEM SOC, V84, P239
[2]   THE GENERATION OF PHASE-SENSITIVE 2D N-15-H-1 SPECTRA USING GRADIENT PULSES FOR COHERENCE-TRANSFER-PATHWAY SELECTION [J].
BOYD, J ;
SOFFE, N ;
JOHN, B ;
PLANT, D ;
HURD, R .
JOURNAL OF MAGNETIC RESONANCE, 1992, 98 (03) :660-664
[3]   EXPERIMENTS FOR RECORDING PURE-ABSORPTION HETERONUCLEAR CORRELATION SPECTRA USING PULSED FIELD GRADIENTS [J].
DAVIS, AL ;
KEELER, J ;
LAUE, ED ;
MOSKAU, D .
JOURNAL OF MAGNETIC RESONANCE, 1992, 98 (01) :207-216
[4]  
GOLDBLATT LA, 1969, AFLATOXIN, P13
[5]  
KURZ M, 1991, ANGEW CHEM INT EDIT, V30, P1329, DOI 10.1002/anie.199113291
[6]   DETERMINATION OF D-AMINO ACIDS .2. USE OF A BIFUNCTIONAL REAGENT, 1,5-DIFLUORO-2,4-DINITROBENZENE [J].
MARFEY, P .
CARLSBERG RESEARCH COMMUNICATIONS, 1984, 49 (06) :591-596
[7]  
MASSEY TE, 1995, P SOC EXP BIOL MED, V208, P213, DOI 10.3181/00379727-208-43852A
[8]   Long-range carbon-proton coupling constants for stereochemical assignment of acyclic structures in natural products: Configuration of the C5-C9 portion of maitotoxin [J].
Matsumori, N ;
Nonomura, T ;
Sasaki, M ;
Murata, M ;
Tachibana, K ;
Satake, M ;
Yasumoto, T .
TETRAHEDRON LETTERS, 1996, 37 (08) :1269-1272
[9]   Stereochemical determination of acyclic structures based on carbon-proton spin-coupling constants. A method of configuration analysis for natural products [J].
Matsumori, N ;
Kaneno, D ;
Murata, M ;
Nakamura, H ;
Tachibana, K .
JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (03) :866-876
[10]   Absolute configuration of amphidinol 3, the first complete structure determination from amphidinol homologues: Application of a new configuration analysis based on carbon-hydrogen spin-coupling constants [J].
Murata, M ;
Matsuoka, S ;
Matsumori, N ;
Paul, GK ;
Tachibana, K .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (04) :870-871