An efficient approach to the multigram synthesis of 2‐((hetera)cyclo)alkylchromanols and their spirocyclic analogs based on enzymatic resolution is described. It is shown that enzymatic acylation could be used for the preparation of enantioenriched title compounds with primary alkyl substituents at the C‐2 position. Meanwhile, enzymatic hydrolysis of the corresponding acetates was optimal for the preparation of the target alcohols when significant steric hindrance is present, e.g., due to the α‐branching. The latter factor was demonstrated to be crucial for the enzymatic reaction rate in both cases. The synthetic utility of the obtained chiral alcohols was demonstrated through Mitsunobu configuration inversion, as well as by preparation of the corresponding primary amines – valuable sp3‐enriched building blocks for medicinal chemistry.

中文翻译：

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通过酶法分离合成对映体富集的 2-（（Hetera）cyclo）烷基色糖醇及其螺环类似物


描述了一种基于酶分辨率的 2-（（hetera）cyclo）烷基色醇及其螺环类似物的多克合成方法。结果表明，酶促酰化可用于制备在 C-2 位具有伯烷基取代基的对映体富集标题化合物。同时，当存在显著的空间位阻时，例如由于α支化，相应乙酸盐的酶促水解是制备目标醇的最佳选择。在这两种情况下，后一个因素都被证明对酶促反应速率至关重要。通过 Mitsunobu 构型反转以及制备相应的伯胺（用于药物化学的有价值的富含 sp3 的构建单元）证明了所获得的手性醇的合成效用。