OsO4•Streptavidin: A Tunable Hybrid Catalyst for the Enantioselective cis-Dihydroxylation of Olefins
OsO4•Streptavidin: A Tunable Hybrid Catalyst for the Enantioselective cis-Dihydroxylation of Olefins
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DOI：
10.1002/anie.201103632
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Ward, Thomas R.
中科院分区：
文献类型：
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作者：
Koehler, Valentin;Mao, Jincheng;Ward, Thomas R.
酶催化和均相催化已经独立发展，以解决合成对映不纯产物的挑战。人工金属酶结合了生物催化剂结构的多样性和丰富的金属催化反应，作为这些领域的补充，越来越受到人们的关注在均相催化中，烯烃的顺式选择性、依赖于oso4的不对称二羟基化反应（AD）是合成邻二醇最有效的方法之一。用于均相催化的配体主要是由Sharpless及其同事开发的，除了少数例外，它们几乎完全基于奎尼丁或奎宁衍生物虽然大多数种类的前手性烯烃是二羟基化的，具有良好的活性和选择性，但顺取代烯烃存在问题。自然界依赖非血红素铁双加氧酶，如萘双加氧酶（NDO）来进行相关反应。这些酶显示出广泛的底物范围据信，oso4和ndo催化的二羟基化反应都是通过外球[3+ 2]机制进行的，在这种机制中，底物不与处于过渡态的金属结合（图1）。[2a, f， 3c]考虑到仿生方法，我们假设在蛋白质中锚定具有催化能力的OsVIII中心可能为烯烃的AD提供人工金属酶。在Kokubo等人的报告的鼓励下[2]，我们开始筛选各种蛋白质，并测试是否可以通过遗传手段优化所得到的二羟化酶。5种蛋白作为α甲基苯乙烯AD的宿主，其中野生型链亲和素（SAV）表现最好。相比之下，牛血清白蛋白（BSA）产生相反的对映体，尽管周转率低（表1）。考虑到蛋白的大小（BSA为66 kDa， SAV单体为16 kDa），重组BSA、[4]的生产难度较大，且BSA、[4]的数量较多
Enzymatic and homogeneous catalysis have evolved independently to address the challenges in the synthesis of enantiopure products. With the aim of complementing these fields, artificial metalloenzymes, which combine the structural diversity of biocatalysts with the wealth of metal-catalyzed reactions, have attracted increasing attention.[1] In homogeneous catalysis the cis-selective, OsO4-dependent asymmetric dihydroxylation (AD) of olefins ranks among the most powerful methods for the synthesis of vicinal diols. Ligands for homogeneous catalysis have been largely developed by Sharpless and co-workers, and are, with few exceptions, almost exclusively based on quinidine or quinine derivatives.[2] Although most classes of prochiral olefins are dihydroxylated with good activity and selectivity, the cissubstituted olefins are problematic. Nature relies on nonheme iron dioxygenases such as naphthalene dioxygenase (NDO) to perform a related reaction. These enzymes display broad substrate scope.[3] It is believed that both the OsO4-and NDO-catalyzed dihydroxylations proceed by an outer sphere [3+ 2] mechanism in which the substrate is not bound to the metal in the transition state (Figure 1).[2a, f, 3c] Considering a biomimetic approach, we hypothesized that anchoring a catalytically competent OsVIII center within a protein might afford an artificial metalloenzyme for the AD of olefins. Encouraged by a report by Kokubo et al.,[2d] we set out to screen various proteins and to test whether the resulting dihydroxylases could be optimized by genetic means.Five proteins were evaluated as hosts for the AD of αmethylstyrene: Wild-type streptavidin (SAV) clearly performed best. In contrast, bovine serum albumin (BSA) yielded the opposite enantiomer, albeit with a low turnover number (Table 1). In view of the size of the proteins (66 kDa for BSA and 16 kDa for the SAV monomer), the difficult recombinant production of BSA,[4] and the number of