生物活性环肽Paecilodepsipeptide A的全合成

Total Synthesis of the Active Cyclodepsipeptides Paecilodepsipeptide A

首次采用逆合成法对昆虫病原真菌Paecilomyces cinnamomeus BCC 9616中分离的高活性抗肿瘤环己肽环肽Paecilodepsipeptide A进行了全合成.采用标准肽化学合成方法,完成了五肽的合成;以酪氨酸甲酯盐酸盐为起始原料,得到O-异戊烯基-D-酪氨酸衍生物;通过五肽与O-异戊烯基-D-酪氨酸衍生物的酯化反应得到环化前体;采取大环内酰氨化和大环内酯化的策略进行关环,完成了天然产物Paecilodepsipeptide A的全合成,产率72%.目标化合物经质谱与核磁共振光谱结构确证与天然产物一致.

Paecilodepsipeptide A isolated from Paecilomyces cinnamorneus BCC 9616 was first synthesized by retrosynthesis method, which shows good antimalarial and antitumor activity. Pentapeptide was synthesized by standard peptide synthesis method at first. Then, O- isopentenyl-D-tyrosine derivatives were obtained by using tyrosine methyl ester hydrochloride as the raw material. The cyclization precursors were obtained by esterification reaction between the pentapeptide and the O-isopentenyl-D-tyrosine derivatives. Finally, the cyclization was achieved and the yield rate of Paecilodepsipeptide A was 72 %. The structures of the synthesized product were identified by 1H NMR and 13C NMR spectra, which is identical to the natural product.