Total synthesis of cryptophycin 3

The depsipeptide cryptophycin 3 (5) and the cryptophycin analogue 43 were prepared from the corresponding four sub-units. The tripeptide analogue 34 was acquired from the starting amino ester 33, which contains fragments D and C. After extension at the carboxyl function by esterification with the hydroxy ester 10, the seco compounds 37 and 42 were obtained. Ring closure was achieved by macrolactamization in the presence of TBTU as condensing agent. This work features a streamlined synthesis of the hydroxy ester 10, a short synthesis of the amino acid 14 by enantioselective alkylation of the glycinimine 21, and the use of the Fmoc protecting group for the amino functions. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).