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

Abstract

International audienceA 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