Abstract: Paecilodepsipeptide A isolated from <em<Paecilomyces cinnamomeus</em< 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, <em<O</em<-isopentenyl-<em<D</em<-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 <em<O</em<-isopentenyl-<em<D</em<-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 <sup<1</sup<H NMR and <sup<13</sup<C NMR spectra, which is identical to the natural product.