Chemical Synthesis of Lipovelutibols B and D and Their Analogues

Abstract

Lipopeptaibols are a group of membrane-active peptides first isolated from cultures of various Trichoderma fungi. Recently, four novel lipopeptaibols named lipovelutibols A-D were isolated from the Himalayan cold habitat fungus T. velutinum. Of them lipovelutibols B and D display cytotoxic activity against certain cell lines such as HL-60 (human leukemia), LS180 (colon cancer), MDA-MB-231 (breast cancer), and A549 (lung cancer). The total synthesis of lipovelutibols B and D and their analogues requires either (i) the immobilisation of leucine on a suitable linker and resin followed by elaboration of the peptide using Fmoc SPPS, followed by cleavage and reduction to the leucinol or (ii) synthesis of leucinol and immobilisation of this building block on resin, followed by SPPS to the lipopeptide. This project aims to confirm the structure of the reported compounds by comparative analysis and study their structure-activity relationships. Following successful synthesis, the analogues will be tested for their activity against cancer cell lines as well as general antimicrobial activity using lipovelutibols B and D as controls.