Spiroligozymes for Transesterifications: Design and Relationship of Structure to Activity
Spiroligozymes for Transesterifications: Design and Relationship of Structure to Activity
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DOI：
10.1021/ja3069648
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发表时间：
2012-11-07
影响因子：
15
通讯作者：
Schafmeister, Christian E.
中科院分区：
文献类型：
--
作者：
Kheirabadi, Mahboubeh;Celebi-Oelcuem, Nihan;Schafmeister, Christian E.
基于酯交换反应的催化剂。采用“由内而外”的设计策略，在立体化学上定义、模块化、功能化的阶梯分子（称为螺旋溶菌酶）上进行设计，并进行综合突变以提高催化能力。首先合成了一系列立体化学和区域化学上不同的双功能螺旋菌酵素，以确定吡啶作为一般碱催化剂和醇亲核试剂加速攻击三氟乙酸乙烯酯作为亲电试剂的最佳排列。最佳双功能螺旋菌酵素与三氟乙酸乙烯酯反应形成酰基-螺旋菌酵素偶联物，反应速度比与苯甲醇反应快2.7 × 10(3)倍。然后合成了两种三功能的螺旋菌酵素，它们将尿素与吡啶和醇结合，作为氧阴离子孔，激活结合的酰基-螺旋菌酵素中间体，使酰基转移到甲醇。最佳的三功能螺溶菌酶可进行多次转化并作为酯交换催化剂，其k(1)/k（uncat）为2.2 X 10(3), k(2)/k（uncat）为1.3 X 10(2)。量子力学计算确定了催化循环的四个过渡态，并提供了酯交换反应每个阶段的详细视图。
Transesterification catalysts based. on stereochemically defined, modular, functionalized ladder-molecules (named spiroligozymes) were designed, using the "inside-out" design strategy, and mutated synthetically to improve catalysis. A series of stereochemically and regiochemically diverse bifunctional spiroligozymes were first synthesized to identify the best arrangement of a pyridine as a general base catalyst and an alcohol nucleophile to accelerate attack on vinyl trifluoroacetate as an electrophile. The best bifunctional spiroligozyme reacted with vinyl trifluoroacetate to form an acyl-spiroligozyme conjugate 2.7 X 10(3)-fold faster than the background reaction with a benzyl alcohol. Two trifunctional spiroligozymes were then synthesized that combined a urea with the pyridine and alcohol to act as an oxyanion hole and activate the bound acyl-spiroligozyme intermediate to enable acyl-transfer to methanol. The best trifunctional spiroligozyme carries out multiple turnovers and acts as a transesterification catalyst with k(1)/k(uncat) of 2.2 X 10(3) and k(2)/k(uncat) of 1.3 X 10(2). Quantum mechanical calculations identified the four transition states of the catalytic cycle and provided a detailed view of every stage of the transesterification reaction.