Enantiodivergent preparation of optically active oxindoles having a stereogenic quaternary carbon center at the C3 position via the lipase-catalyzed desymmetrization protocol: effective use of 2-furoates for either enzymatic esterification or hydrolysis.
Enantiodivergent preparation of optically active oxindoles having a stereogenic quaternary carbon center at the C3 position via the lipase-catalyzed desymmetrization protocol: effective use of 2-furoates for either enzymatic esterification or hydrolysis.
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DOI：
10.1021/jo035749h
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发表时间：
2004-03
期刊：
影响因子：
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通讯作者：
S. Akai;Toshiaki Tsujino;Emi Akiyama;Kouichi Tanimoto;T. Naka;Y. Kita
中科院分区：
文献类型：
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作者：
S. Akai;Toshiaki Tsujino;Emi Akiyama;Kouichi Tanimoto;T. Naka;Y. Kita
羟吲哚 2a-h 的两种对映体均在 C3 位点具有立体季碳中心和不同的 N 保护基团，可通过脂肪酶催化的去对称化方案轻松制备。因此，前手性二醇 3a-h 与 1-乙氧基乙烯基 2-糠酸酯 5 被假丝酵母脂肪酶催化，得到 (R)-(+)-2a-h (68-99% ee)，其中混合溶剂 (i)Pr(2)O (二异丙醚)-THF 的使用至关重要。相同的脂肪酶还在(i)Pr(2)O、THF和H(2)O的混合物中实现二糠酸酯4a-h的对映选择性水解，以提供对映体(S)-(-)-2a-h(82-99％ee)。通过两种方法获得的产物2对于外消旋作用都是稳定的。这些酶促去对称反应也适用于其他典型的对称二糠酸酯12b和15b，以提供抗外消旋化的产物13b和16b。
Both enantiomers of oxindoles 2a-h, having a stereogenic quaternary carbon center at the C3 position and a different N-protective group, were readily prepared by the lipase-catalyzed desymmetrization protocol. Thus, the transesterification of the prochiral diols 3a-h with 1-ethoxyvinyl 2-furoate 5 was catalyzed by Candida rugosa lipase to give (R)-(+)-2a-h (68-99% ee), in which the use of a mixed solvent, (i)Pr(2)O (diisopropyl ether)-THF, was crucial. The same lipase also effected the enantioselective hydrolysis of the difuroates 4a-h in a mixture of (i)Pr(2)O, THF, and H(2)O to provide the enantiomers (S)-(-)-2a-h (82-99% ee). The products 2 obtained by both methods were stable against racemization. These enzymatic desymmetrization reactions were also applicable for other typical symmetrical difuroates 12b and 15b to provide the racemization-resistant products 13b and 16b.