Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus.
Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus.
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黄曲霉素 A 的绝对构型，是寄生曲霉产生黄曲霉毒素的特异性抑制剂。
DOI：
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发表时间：
2000
影响因子：
3.6
通讯作者：
S. Sakuda
中科院分区：
文献类型：
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作者：
H. Ikeda;N. Matsumori;M. Ono;A. Suzuki;A. Isogai;H. Nagasawa;S. Sakuda
Aflastatin A(1)是寄生曲霉产生黄曲霉毒素的特异性抑制剂。它具有具有长烷基侧链的四酸衍生物的新颖结构。本研究从化学角度阐明了1中29个手性中心的绝对构型。首先，从1或其甲醚(2)合成了4个小片段分子，其绝对结构分别为N-甲基-D-丙氨酸、(2S，4R)-2，4-二甲基-1，6-己二醇二苯甲酸酯、(R)-3-羟基十二酸和(R)-1，2，4-丁三醇三苯甲酸酯。其次，从1经NaIO(4)氧化得到具有13个手性中心的无环碎片分子3，并通过J构型分析确定了其相对立体化学结构。通过分析(3)J(H，H)和(2，3)J(C，H)的耦合常数和ROE数据，验证了3的相对构型。最后，通过对由2制备的含有28个手性碳的碎片分子7的进一步J基构型分析，阐明了1的烷基侧链上的所有相对构型。通过将这些相对构型与前四个片段分子的绝对构型联系起来，完全确定了1的绝对立体化学。
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.