A Practical and Efficient Total Synthesis of Potent Insulinotropic (2S,3R,4S)-4-Hydroxyisoleucine through a Chiral N-Protected γ-Keto-α-aminoester

被引：17

作者：

Marin, Sandra De Lamo ^{[1
]}

Catala, Cedric ^{[1
]}

Kumar, Sreekantha Ratna ^{[1
]}

Valleix, Alain ^{[2
]}

Wagner, Alain ^{[1
]}

Mioskowski, Charles ^{[1
]}

机构：

[1] Fac Pharm, Lab Funct ChemoSyst, UMR 7199, F-67400 Illkirch Graffenstaden, France

[2] CEA, Serv Mol Marquees, F-91191 Gif Sur Yvette, France

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2010年 / 2010卷 / 21期

关键词：

Amino acids; Organocatalysis; Asymmetric synthesis; Chiral resolution; Total synthesis; MANNICH-TYPE REACTIONS; 3-PYRROLIDINECARBOXYLIC ACID; FENUGREEK SEEDS; 4-HYDROXYISOLEUCINE; DERIVATIVES; ANALOGS;

D O I：

10.1002/ejoc.201000378

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

(2S,3R,4S)-4-Hydroxyisoleucine, which exhibits remarkable insulinotropic activity, is expected to be a potent drug to treat type II diabetes. We propose herein a four-step synthesis of the enantiopure natural product on the basis of successive Mannich condensation, catalytic epimerization, N-paramethoxyphenyl deprotection, and diastereoselective reduction. This compact economical and scalable sequence enables to perfectly control three contiguous chiral centers, It does not involve any chromatographic purification, and the desired compound is obtained in >99 %de, >99 % ee, and 22% overall yield under our optimized conditions.

引用

页码：3985 / 3989

页数：5

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