Total Synthesis of (+)-Silybin A

Makoto Inai; Hiroto Sagara; Yoshinori Ueno; Hitoshi Ouchi; Fumihiko Yoshimura; Tomohiro Asakawa; Yoshitaka Hamashima; Toshiyuki Kan

doi:10.1248/cpb.c24-00276

Total Synthesis of (+)-Silybin A

Chem Pharm Bull (Tokyo). 2024;72(6):570-573. doi: 10.1248/cpb.c24-00276.

Authors

Makoto Inai¹, Hiroto Sagara¹, Yoshinori Ueno¹, Hitoshi Ouchi¹, Fumihiko Yoshimura¹, Tomohiro Asakawa², Yoshitaka Hamashima¹, Toshiyuki Kan¹

Affiliations

¹ School of Pharmaceutical Sciences, University of Shizuoka.
² School of Marine Science and Technology, Tokai University.

PMID: 38910121
DOI: 10.1248/cpb.c24-00276

Abstract

We report the first total synthesis of silybin A (1). Key synthetic steps include the construction of the 1,4-benzodioxane neolignan skeleton, a modified Julia-Kocienski olefination reaction between m-nitrophenyltetrazole sulfone (m-NPT sulfone) 10 and aldehyde 21, the formation of the flavanol lignan skeleton 28 via a quinomethide intermediate under acidic conditions, and stepwise oxidation of the benzylic position of flavanol 29.

Keywords: hybrid polyphenol; modified Julia–Kocienski olefination; quinomethide; silybin A; total synthesis.

MeSH terms

Molecular Structure
Oxidation-Reduction
Silybin* / chemical synthesis
Silybin* / chemistry
Silymarin / chemical synthesis
Silymarin / chemistry
Stereoisomerism

Substances

Silybin
Silymarin