ENANTIOSELECTIVE ENZYMATIC AMINOLYSIS AND AMMONOLYSIS OF DIMETHYL 3-HYDROXYGLUTARATE. SYNTHESIS OF (R)-4-AMINO-3-HYDROXYBUTANOIC ACID
ENANTIOSELECTIVE ENZYMATIC AMINOLYSIS AND AMMONOLYSIS OF DIMETHYL 3-HYDROXYGLUTARATE. SYNTHESIS OF (R)-4-AMINO-3-HYDROXYBUTANOIC ACID
复制标题
对映选择性酶促氨解和 3-羟基戊二酸二甲酯的氨解。
DOI：
10.1021/jo960468d
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发表时间：
1996
影响因子：
3.6
通讯作者：
V. Gotor
中科院分区：
文献类型：
--
作者：
Susana Puertas;F. Rebolledo;V. Gotor
酶现在被广泛认为是不对称合成的实用催化剂，它们区分对映异构体或前手性分子表面的能力尤为重要。水解、酯交换或内酯化已被应用于前手性二酯和二醇，以制备高光学纯度的手性合成物。然而，酶，特别是脂肪酶，催化前手性底物的氨解的潜力迄今尚未研究。考虑到这一点，本工作的主要目的是研究一种前手性二酯，3-羟戊二酸二甲酯的氨解和氨解反应(1)。1的光学活性衍生物已被证明在天然产物的合成中的效用；例如(R)和(S)-3-羟基戊二酸单烷基酯是合成海马苷、压实素的内酯部分3和其他美维酸的起始原料。4此外，1的氨解和氨解衍生的化合物，由于它们具有酰胺功能，可能是生物活性氨基酸、氨基醇和其他多功能化化合物的合适前体。我们选择了来自南极念珠菌（Candida antarctica， CAL）的脂肪酶作为生物催化剂，该酶在通过氨解和氨解过程拆分手性酯和手性胺及二胺方面已经显示出很高的效率。
Enzymes are now widely recognized as practical catalysts for asymmetric synthesis, 1 their abilities to discriminate between enantiotopic groups or faces of a prochiral molecule being of particular importance. Hydrolysis, transesterification, or lactonization processes2 have been applied to prochiral diesters and diols in order to prepare chiral synthons of high optical purity. However, the potential of enzymes, especially lipases, to catalyze the aminolysis of prochiral substrates has not hitherto been investigated.With this in mind, the main purpose of this work is the study of the aminolysis and ammonolysis reactions of a prochiral diester, dimethyl 3-hydroxyglutarate (1). Optically active derivatives of 1 have proven utility in the synthesis of natural products; for example (R)-and (S)-3-hydroxyglutaric acid monoalkyl esters are starting materials in the synthesis of pimaricin, 3 the lactone portion of compactin, and other mevinic acids. 4 In addition, compounds derived of the aminolysis and ammonolysis of 1, since they bear an amide function, could be suitable precursors of biologically active amino acids, amino alcohols, and other polyfunctionalized compounds. We have chosen as biocatalyst the lipase from Candida antarctica (CAL), which has shown already a great efficiency in the resolution of both chiral esters5 and chiral amines and diamines6 through aminolysis and ammonolysis processes.