Development of a Convergent Enantioselective Synthetic Route to (-)-Myrocin G.

ABSTRACT: Myrocins are a family of antiproliferative antibiotic fungal metabolites possessing a masked electrophilic cyclopropane. Preliminary chemical reactivity studies imputed the bioactivity of these natural products to a DNA cross-linking mechanism, but this hypothesis was not confirmed by studies with native DNA. We recently reported a total synthesis of (-)-myrocin G (4), the putative active form of the metabolite myrocin C (1), that featured a carefully orchestrated tandem fragment coupling-annulation cascade. Herein, we describe the evolution of our synthetic strategy toward 4 and report the series of discoveries that prompted the design of this cascade coupling. Efforts to convert the diosphenol (-)-myrocin G (4) to the corresponding 5-hydroxy-γ-lactone isomer m

SUBMITTER: Tomanik M 

PROVIDER: S-EPMC7520802 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature