Year: 2024
Type: article
Abstract: Thiosilvatins are a family of biologically active sulfenylated diketopiperazine natural products. The first members were reported over 40 years ago, but total synthesis of a thiosilvatin has remained elusive. Here, we describe the first, collective, synthesis of the parent epidithiodiketopiperazine (-)-dithiosilvatin and ten related thiosilvatins. Several of the targets are structurally revised. A catalytic asymmetric sulfenylation of triketopiperazines efficiently controls absolute configuration at the thioaminal units. Further synthetic highlights include a diastereoconvergent installation of the requisite cis-orientation of the sulfur atoms and a tandem epidisulfide formation/O-prenylation under mild Mitsunobu conditions. The described methods for late-stage diversification of sensitive bis(methylthio)diketopiperazines offer a blueprint for systematically exploring this interesting 3D-pharmacophore in stereochemically pure form.
Authors: Jian Liu, Robin Ekberg, Nicolas R. Koning, Daniel Strand
Institution: Lund University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,510
Funders: Wenner-Gren Stiftelserna, Vetenskapsrådet
OpenAlex ID: W4401704434