Total Synthesis of Cyclosenegalin A

Abstract

A Pro‐Gly‐typed cyclopeptide, cyclosenegalin A, was firstly isolated from Annona senegalensis and Annona scleroderma. In this study, we reported synthesis the cycloheptapeptide with a combination of solid‐ and solution‐phase synthetic methods. This study also compared the effectiveness of β‐turn inducer type I and II in cyclosenegalin A to facilitate the cyclization process. The synthesis of cyclosenegalin A were prepared using two different sequences of linear peptides for cyclization. First sequence employed β‐turn type I inducer (Ser‐Ala‐Val‐Thr) as turning point and second sequence employed β‐turn type II inducer (Thr‐Pro‐Gly‐Leu). The successful cyclization was obtained using the linear sequence of NH2‐Ala‐Val‐Thr‐Pro‐Gly‐Leu‐Ser‐OH with β‐turn type II. The final product was obtained in 8.2 % yield with PyBOP/DIEA act as coupling agent. The synthetic cyclosenegalin A were characterized with HR‐ToFMS, 1H NMR, 13C NMR, HSQC, HMBC, TOCSY, and ROESY. The synthetic product was also evaluated for its antimicrobial activity.