Selective access to both cis- and trans-isomers of α-substituted 3-hydroxycyclobutane-1-carboxylic esters has been demonstrated using ketoreductase (KRED) enzymes. Two stereocomplementary KREDs were identified from a commercial panel that are highly selective for small α-substituents when the ester group was para-methoxybenzyl. Probing the substrate scope of these two enzymes revealed that the selectivity declined rapidly with both when increasing the steric bulk of the α-substituent. For methyl ester substrates with larger α-substituents, a different pair of KREDs was identified with excellent selectivity for both the cis- and trans-isomers for a small range of substrates. The cyclobutanol products serve as precursors to other synthetically useful building blocks such as amino acids.

中文翻译：

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酮还原酶介导的 1,1-二取代环丁烷-3-醇的立体发散合成


使用酮还原酶 (KRED) 已证明可以选择性地获得 α-取代的 3-羟基环丁烷-1-羧酸酯的顺式和反式异构体。从商业小组中鉴定出两种立体互补的 KRED，当酯基为对甲氧基苄基时，它们对小 α-取代基具有高度选择性。探索这两种酶的底物范围表明，当增加 α-取代基的空间体积时，两者的选择性迅速下降。对于具有较大 α-取代基的甲酯底物，鉴定出一对不同的 KRED，对小范围底物的顺式和反式异构体具有出色的选择性。环丁醇产品可作为其他合成有用的结构单元（例如氨基酸）的前体。