Double-cuvette ISES: In situ estimation of enantioselectivity and relative rate for catalyst screening
Double-cuvette ISES: In situ estimation of enantioselectivity and relative rate for catalyst screening
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DOI：
10.1021/ja052010b
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发表时间：
2005-06-22
影响因子：
15
通讯作者：
Berkowitz, DB
中科院分区：
文献类型：
--
作者：
Dey, S;Karukurichi, KR;Berkowitz, DB
描述了一种新的方法，用于筛选一系列催化剂，原位，估计对映选择性和相对速率。我们将这种方法称为“双比色皿ISES（原位酶筛选）”。Co（III）-salen介导的（±）-环氧丙烷的水解动力学拆分（HKR）用作模型反应以证明原理的证明。在两个平行的比色皿中，将环氧化物和手性salen催化剂装载在较低的基于CHCl 3的有机层中。含水报告层，含有不同的“报告酶”和它们的烟酰胺辅因子，分层以上的有机层。由手性催化剂形成的1，2-丙二醇对映体扩散到水层中，并在那里被报告酶氧化，氧化速率取决于二醇浓度、二醇的R：S比和报告酶的对映体选择性。以氨基酸、萜类化合物和糖类化合物骨架中的7种手性1，2-二胺和7种水杨醛衍生物为原料，构建了一个聚焦手性Salen文库。双比色皿ISES确定了一对夫妇的有趣的组合命中在这个萨伦阵列，其中无论是一个给定的手性二胺的对映选择的意义或幅度显着取决于选择的“水杨醛”的合作伙伴。使用这种新的筛选工具与那些独立测量的预测ee的和相对速率的比较。
Described is a new method for the screening of an array of catalysts, in situ, to estimate enantioselectivity and relative rates. We term this approach “double-cuvette ISES (in situ enzymatic screening)”. The Co(III)-salen mediated hydrolytic kinetic resolution (HKR) of (±)-propylene oxide is used as a model reaction to demonstrate proof of principle. In two parallel cuvettes, a lower CHCl3-based organic layer is loaded with the epoxide and the chiral salen catalyst. Aqueous reporting layers, containing distinct “reporting enzymes” and their nicotinamide cofactors, are layered above the organic layers. The 1,2-propanediol enantiomers formed by the chiral catalyst diffuse into the aqueous layer and are oxidized there by the reporting enzymes at rates dependent upon the diol concentration, theR:Sratio of the diol, and the enantioselectivity of the reporting enzymes. A focused chiral salen library was constructed from seven chiral 1,2-diamines, derived from amino acid, terpenoid, and carbohydrates skeletons, and seven salicylaldehyde derivatives. Double-cuvette ISES identified a couple of interesting combinatorial hits in this salen array, wherein either the sense or magnitude of enantioselection for a given chiral diamine depends significantly upon the choice of “salicylaldehyde” partner. A comparison of predicted ee's and relative rates using this new screening tool with those independently measured is provided.