Sharma Manik, Li Yue, Biegasiewicz Kyle F
Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
Org Lett. 2025 Jun 6;27(22):5584-5588. doi: 10.1021/acs.orglett.5c01137. Epub 2025 May 20.
Thioketals are an important class of molecules used for the preparation and protection of carbonyl compounds in chemical synthesis. Selective cleavage of thioketals requires the use of harsh conditions and reagents that limit the use of thioketals in chemoenzymatic synthesis. Herein, we describe a biocatalytic strategy for the cleavage of thioketals using enzymatic bromide recycling by vanadium-dependent haloperoxidase (VHPO) enzymes. This reaction design involves halogenation-mediated thioketal cleavage through repetitive enzyme-mediated formation of hypobromous acid with a catalytic quantity of bromide salt and hydrogen peroxide as the terminal oxidant. This protocol is demonstrated on a broad range of 1,3-dithiolanes in high yield and excellent chemoselectivity, performed on a gram scale, run with lysate and whole cells, and applied to the cleavage of 1,3-dithianes and 1,3-oxathiolanes.
硫代缩酮是化学合成中用于制备和保护羰基化合物的一类重要分子。硫代缩酮的选择性裂解需要使用苛刻的条件和试剂，这限制了硫代缩酮在化学酶促合成中的应用。在此，我们描述了一种生物催化策略，利用钒依赖性卤过氧化物酶（VHPO）进行酶促溴化物循环来裂解硫代缩酮。该反应设计涉及通过重复的酶介导的次溴酸形成（以催化量的溴化物盐和过氧化氢作为终端氧化剂）实现卤化介导的硫代缩酮裂解。该方案在多种1,3 - 二硫戊环上以高产率和优异的化学选择性得到了验证，可在克级规模上进行，使用裂解物和全细胞进行操作，并应用于1,3 - 二噻烷和1,3 - 氧硫杂环戊烷的裂解。
