A Practical Synthesis of (2S,3R,4S)-4-Hydroxyisoleucine, A Potent Insulinotropic α-Amino Acid from Fenugreek

Abstract

An efficient eight-step synthesis of optically pure (2S,3R,4S)-4-hydroxyisoleucine (1), a potent insulinotropic α-amino acid found in the seeds of fenugreek (Trigonella foenum-graecum L.), is achieved in 39% overall yield. The method is suitable for large-scale production of the title compound. The key steps involve the biotransformation of ethyl 2-methylacetoacetate to ethyl (2S,3S)-2-methyl-3-hydroxybutanoate (2) with Geotrichum candidum and an asymmetric Strecker synthesis. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)