Synthesis of menarandroside A from dehydroepiandrosterone

Abstract

Menarandroside A, which bears a 12α-hydroxypregnenolone steroid backbone, was isolated from the plant, Cynanchum menarandrense. Treatment of extracts from this plant containing menarandroside A against secretin tumor cell line (STC-1) intestinal cells, resulted in an increased secretion of glucagon-like peptide 1 (GLP-1), a peptide that plays a role in the regulation of blood sugar levels. Increase in GLP-1 is beneficial for the treatment of type 2 diabetes. We disclose the synthesis of menarandroside A from dehydroepiandrosterone (DHEA). Key features of this synthesis include: (i) Wittig reaction of the C17-ketone of a 12-oxygenated DHEA derivative to introduce the C17-acetyl moiety, and (ii) the stereoselective reduction of a C12-keto intermediate bearing an sp²-center at C17 to yield the C12α-hydroxy group. In addition, an oxidation of a methyl enol ether derivative to an α-hydroxy methyl ester using tetrapropylammonium perruthenate (TPAP) and N-methyl-morpholine-N-oxide (NMO) was discovered.