Cruz Luis J, Cuevas Carmen, Cañedo Librada M, Giralt Ernest, Albericio Fernando
Barcelona Biomedical Research Institute, Barcelona Science Park, University of Barcelona, 08028-Barcelona, Spain.
J Org Chem. 2006 Apr 28;71(9):3339-44. doi: 10.1021/jo051601h.
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-Me2Leu, 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.
通过合成设计、正交保护基和偶联试剂的适当组合，完成了天然海洋环缩肽IB-01212的首次已知合成。这种环状对称八肽包含以下每种残基各两个：L-N，N-二甲基亮氨酸、L-丝氨酸、L-N-甲基亮氨酸和L-N-甲基苯丙氨酸。IB-01212在丝氨酸的羟基与N-甲基苯丙氨酸的羧基之间还具有两个对称酯键。该产物的全固相合成通过三条不同路线并行进行：杂肽片段的二聚化、线性合成和汇聚合成。就产物收率和纯度而言，汇聚策略取得了最佳结果，特别适合于IB-01212及类似肽的大规模合成。
