Total synthesis of the natural HDAC inhibitor Cyl-1. Issue 18 (24th April 2018) - Servatius, Phil
Abstract : A chelate enolate Claisen rearrangement was used as a key step in the first total synthesis ofCyl-1, a cyclic tetrapeptide from Cylindrocladium scoparium . Abstract : Chelate enolate Claisen rearrangements are powerful reactions for constructing amino acid scaffolds. They generally proceed via chair-like transition states with excellent transfer of stereogenic information. Utilizing this reaction in natural product synthesis gives access to non-proteinogenic amino acids such as (2 S, 9 S )-2-amino-8-oxo-9, 10-epoxydecanoic acid (Aoe), the unusual amino acid of a series of histone deacetylase inhibitors (HDACi). Herein the first total synthesis ofCyl-1, a cyclotetrapeptide from Cylindrocladium scoparium, is described.