Multi-Step Synthesis and Biological Evaluation of Analogues of Insulin Secretagogue (2S,3R,4S)-4-Hydroxyisoleucine

被引：11

作者：

Aouadi, Kaiss ^{[1
,2
,3
]}

Lajoix, Anne-Dominique ^{[4
,5
]}

Gross, Rene ^{[4
,5
]}

Praly, Jean-Pierre ^{[1
,2
,3
]}

机构：

[1] Univ Lyon, CNRS, Inst Chim & Biochim Mol & Supramol, UMR 5246,Lab Chim Organ 2, F-69622 Villeurbanne, France

[2] Univ Lyon 1, F-69622 Villeurbanne, France

[3] CPE Lyon, F-69616 Villeurbanne, France

[4] Univ Montpellier 1, CNRS, UMR 5232, Fac Pharm,Ctr Pharmacol & Innovat Diabet, F-34093 Montpellier, France

[5] CNRS, UMR 5232, F-34093 Montpellier, France

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2009年 / 2009卷 / 01期

关键词：

Carbohydrates; Lactones; Nucleophilic substitution; Amino acids; Biological activity; GLYCOGEN-PHOSPHORYLASE INHIBITORS; 1,3-DIPOLAR CYCLOADDITION REACTIONS; ASYMMETRIC ALDOL REACTIONS; TRIGONELLA-FOENUM-GRAECUM; C-GLYCOSYL COMPOUNDS; ALPHA-AMINO-ACIDS; ENANTIOSELECTIVE SYNTHESIS; D-RIBONOLACTONE; GAMMA-LACTONES; STEREOSELECTIVE SYNTHESIS;

D O I：

10.1002/ejoc.200800744

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A series of stereochemically defined analogues of (2S,3R,4S)4-hydroxyisoleucine and related alpha-hydroxy acids have been prepared by multi-step routes from D-glucose, whereas ketolization between TBDMS-protected hydroxypropanone and ethyl isocyanoacetate led to racemic analogues. Bioassays showed that of eight newly synthesized Compounds, two of them presented an interesting statistical trend to increase glucose-induced insulin secretion when tested in isolated rat pancreatic islets in the presence of 8.3 mM glucose and at a concentration of 200 pm, which has previously been shown to be effective for (2S,3R,4S)-4-hydroxyisoleucine, ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

引用

页码：61 / 71

页数：11

共 75 条

[1] STEREOCHEMISTRY OF THE 4-HYDROXYISOLEUCINE FROM TRIGONELLA-FOENUM-GRAECUM [J].