Collective Asymmetric Synthesis of Thiosilvatins.

Liu, Jian; Ekberg, Robin; Koning, Nicolas R; Strand, Daniel

Liu, Jian; Ekberg, Robin; Koning, Nicolas R; Strand, Daniel.

Afiliación

Liu J; Lund University, Department of Chemistry, SWEDEN.
Ekberg R; Lund University, Department of chemistry, SWEDEN.
Koning NR; Lund University, Department of Chemistry, SWEDEN.
Strand D; Lunds Universitet, Department of Chemistry, Centre for Analysis and Synthesis, Box 124, 221 00, Lund, SWEDEN.

Angew Chem Int Ed Engl ; : e202412397, 2024 Aug 19.

Article en En | MEDLINE | ID: mdl-39157913

ABSTRACT

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.

Palabras clave

Diastereoconvergent synthesis; Epidithiodiketopiperazines; natural products; organocatalysis; total synthesis

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Angew Chem Int Ed Engl Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Alemania

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