2004 年 62 巻 9 号 p. 882-894
Three approaches to biotin (1), i.e., the Cyanohydrin method and the Strecker methods I and II, have been investigated with L-cysteine as a starting material and the last one was found to be so efficient to be applied to a multi-kilogram-scale preparation. α-Amino aldehyde 46, which was readily derived from L-cysteine, was subjected to the Strecker reaction to afford syn-α-amino nitrile 47 with high diastereoselectivity and in high yield. The compound 47 was converted to amide 48 in high yield by applying Katritzky's protocol. Novel S, N-carbonyl migration of 48 and subsequent hydrolysis enabled clean conversion to 37 that is a precursor to a key intermediate 38 for 1. The Fukuyama coupling reaction of 38 with a zinc reagent by the use of our modified procedure employing heterogeneous Pearlman's catalyst allowed efficient installation of the 4-carboxybutyl chain. Short steps, high yield, and ease of operation of the present approach would permit the hitherto most efficient access to 1.