Cbz-N-methyl-L-valine

Grassypeptolide A is a 31-membered cyclodepsipeptide isolated from the marine cyanobacterium Lyngbya confervoides, which exhibits potent anticancer activity. The synthesis was achieved in 17 linear steps with an overall yield of 11.3%. The synthesis employed Cbz-N-methyl-L-valine as a key building block in the preparation of fragment 13. Specifically, Cbz-N-methyl-L-valine (16) was coupled with L-proline tert-butyl ester (17) to form dipeptide 18 in 84% yield, which was subsequently elaborated into the hydroxy acid fragment 13. The bis(thiazoline)-containing fragment 39 was assembled via a series of coupling and thioacylation steps, and the two fragments were united through esterification using the acyl chloride of acid 40. After macrocyclization and global deprotection, selective cyclodehydration of β-hydroxy thioamides using DAST and Troc protection of the secondary alcohol enabled the formation of the bis(thiazoline) rings without epimerization.

Fig. 1 Cbz-N-methyl-L-valine for the synthesis of Fragment 13. (Liu H.; et al. 2013)