Total Solid-Phase Synthesis of Marine Cyclodepsipeptide IB-01212

摘要

A suitable combination of synthetic design,orthogonal protecting groups and coupling reagents was used to complete the first known synthesis of the natural marine Cyclodepsipeptide IB-01212.The cyclic,symmetric octapeptide contains two of each of the following residues:L-N,N-Me_2Leu,L-Ser,L-N-MeLeu and L-N-MePhe.IB-01212 also features two symmetric ester bonds between the hydroxyl group of Ser and the carboxyl function of the N-MePhe.Total solid-phase syntheses of the product was performed in parallel via three distinct routes:dimerization of heterodetic fragments,linear synthesis,and convergent synthesis.The convergent strategy gave the best results in terms of product yield and purity and is particularly suitable for the large-scale synthesis of IB-01212 and similar peptides.