State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, P.R. China.
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin, 300308, P.R. China.
Chemistry. 2022 Nov 2;28(61):e202201997. doi: 10.1002/chem.202201997. Epub 2022 Aug 31.
Chiral sulfoxides are versatile synthons and have gained a particular interest in asymmetric synthesis of active pharmaceutical and agrochemical ingredients. Herein, a linear oxidation-reduction bienzymatic cascade to synthesize chiral sulfoxides is reported. The extraordinarily stable and active vanadium-dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) was used to oxidize sulfides into racemic sulfoxides, which were then converted to chiral sulfoxides by highly enantioselective methionine sulfoxide reductase A (MsrA) and B (MsrB) by kinetic resolution, respectively. The combinatorial cascade gave a broad range of structurally diverse sulfoxides with excellent optical purity (>99 % ee) with complementary chirality. The enzymatic cascade requires no NAD(P)H recycling, representing a facile method for chiral sulfoxide synthesis. Particularly, the envisioned enzymatic cascade not only allows CiVCPO to gain relevance in chiral sulfoxide synthesis, but also provides a powerful approach for (S)-sulfoxide synthesis; the latter case is significantly unexplored for heme-dependent peroxidases and peroxygenases.
手性亚砜是多功能的合成子，在手性药物和农用化学品有效成分的不对称合成中引起了特别关注。本文报道了一种用于合成手性亚砜的线性氧化还原双酶级联反应。使用来自新月弯孢（Curvularia inaequalis）的异常稳定和活性的钒依赖型氯化过氧化物酶（CiVCPO）将硫化物氧化成外消旋亚砜，然后通过高度对映选择性的甲硫氨酸亚砜还原酶 A（MsrA）和 B（MsrB）分别通过动力学拆分将其转化为手性亚砜。组合级联反应得到了广泛的具有优异光学纯度（>99%ee）和互补手性的结构多样的亚砜。该酶级联反应不需要 NAD(P)H 循环，代表了一种用于手性亚砜合成的简便方法。特别地，预期的酶级联反应不仅使 CiVCPO 在手性亚砜合成中具有相关性，而且为（S）-亚砜合成提供了一种有力的方法；对于血红素依赖的过氧化物酶和过氧酶，后一种情况的研究还很少。
