First Total Synthesis and Biological Screening of a Proline-Rich Cyclopeptide from a Caribbean Marine Sponge.

Rajiv Dahiya,Suresh Chennupati,Ajay Sharma,Sandeep Maharaj,Sunil Singh

doi:10.3390/md14120228

Abstract

A natural heptacyclopeptide, stylissamide G (7), previously isolated from the Bahamian marine sponge Stylissa caribica from the Caribbean Sea, was synthesized via coupling of the tetrapeptide l-phenylalanyl-l-prolyl-l-phenylalanyl-l-proline methyl ester with the tripeptide Boc-l-leucyl-l-isoleucyl-l-proline, followed by cyclization of the linear heptapeptide fragment. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FT-IR, 1H NMR, 13C NMR and mass spectrometry. Results of pharmacological activity studies indicated that the newly synthesized cycloheptapeptide displayed good anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniea at 2 mg/mL and in addition, potent antifungal activity against pathogenic Candida albicans and dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL.

Highlights

Marine natural products with unique structural features and pronounced biological activities continue to provide leading structures in the search for new drugs from nature [1]
The synthesis of cyclooligopeptide 7 was accomplished with 86% yield, and pyridine proved to be an effective base for cyclization of the linear heptapeptide unit
An efficient strategy was developed toward the first total synthesis of the natural cyclopolypeptide stylissamide G (7) and for the preparation of its unusual linear tetrapeptide, tripeptide and heptapeptide (4–6) building blocks via coupling reactions utilizing carbodiimide chemistry in the alkaline environment in the presence of racemization suppressing agent

Summary

Introduction

Marine natural products with unique structural features and pronounced biological activities continue to provide leading structures in the search for new drugs from nature [1]. Invertebrates such as sponges, tunicates and mollusks have so far provided the largest number of marine-derived secondary constituents. Cyclopolypeptides are a unique group of bioactive compounds with interesting pharmacological and biochemical properties which occur mainly in marine sponges and higher plants [3,4]. Detailed investigation of structures and biological potential of naturally occurring cyclooligopeptides suggests that there are cyclic peptide molecules (as reported in literature) with structural patterns containing two proline units separated by one or more phenylalanine units, and

Methods

Results

Discussion

Conclusion