A facile synthesis and enzymatic resolution of naturally occurring remotely functionalized alkylmethylmaleic anhydrides from Aspergillus wentii:: Aspergillus acids A-D
A facile synthesis and enzymatic resolution of naturally occurring remotely functionalized alkylmethylmaleic anhydrides from Aspergillus wentii:: Aspergillus acids A-D
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DOI：
10.1055/s-2006-926326
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发表时间：
2006-03-02
影响因子：
2.6
通讯作者：
Argade, NP
中科院分区：
文献类型：
--
作者：
Easwar, S;Argade, NP
本文首次报道了四种新的天然存在的远程官能化的次级霉菌代谢物酸酐lad的合成，以N-对甲苯基柠康酰亚胺（5）为起始原料，经三至六步反应，总收率为20-65%。三苯基膦-马来酰亚胺加成物6与醛4缩合得到外酰亚胺7，经异构化、水解、酰化得到曲霉酸A（1a），四步总收率54%。加合物6与醛15的缩合类似地在两个步骤中得到所需的酰亚胺17。酰亚胺17的酸催化水解直接得到曲霉酸B（1 B），暴露出作为末端乙炔存在的潜在甲基酮。硼氢化钠诱导曲霉酸B（1 B）化学选择性还原，得到曲霉酸C（1c），经醋酸酐诱导酰化，得到曲霉酸D（1d）。在Amano PS催化下，曲霉酸C（1c）的酰化反应得到（+）-曲霉酸C（1 e）和（-）-曲霉酸D（1f），收率分别为70%ee和72%ee。
The first synthesis of four new naturally occurring remotety functionalized secondary mould metabolite anhydrides lad is described starting from N-p-tolyl citraconimide (5) in three to six steps and 20-65% overall yields. The condensation of triphen-ylphosphine-maleimide adduct 6 with aldehyde 4 furnished the exoimide 7, which after isomerization, hydrolysis, and acylation gave aspergillus acid A (1a) in 54% overall yield ill four steps. The condensation of adduct 6 with aldehyde 15 similarly afforded the desired imide 17 in two steps. The acid-catalyzed hydrolysis of imide 17 directly furnished aspergillus acid B (1b), exposing the latent methyl ketone present as the terminal acetylene. Sodium borohydride induced chemoselective reduction of aspergillus acid B (1b) gave aspergillus acid C (1c), which upon acetic anhydride induced acylation, furnished aspergillus acid D (1d). A facile Amano PS catalyzed acylation of aspergillus acid C (1c) gave, in good yield, the desired (+)-aspergillus acid C (1e) in 70% ee and (-)-aspergillus acid D (1f) in 72% ee. In the present enzymatic reaction, the anhydride moiety presumably plays a crucial role in the substrate recognition, binding, and resolution process.