Synthetic study of strongylophorines: stereoselective construction of the characteristic lactone bridge. Issue 35 (31st August 2016)

• Record Type: Journal Article
• Authors: Oikawa, Yuya; Uchiyama, Daiki; Shirasawa, Takuya; Oikawa, Masato; Ishikawa, Yuichi
• Is Part Of: Tetrahedron letters. Volume 57:Issue 35(2016)
• Page Start: 3949
• Page End: 3951
• Publication Date: 2016-08-31
• Subjects: Strongylophorines -- Meroditerpenoid -- Hypoxia inducible factor-1 -- C–H functionalization -- δ-Lactone bridge; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.07.067
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Strongylophorine-2 is a meroditerpenoid isolated from marine sponge, Strongylophora durissima . This compound is an inhibitor for HIF-1 transcriptional pathway. Oxidative C–H functionalization at the C24 methyl group proceeded smoothly. Construction of the C4 quaternary carbon stereogenic center was accomplished. The characteristic lactone bridge was constructed in a stepwise manner. Abstract: Herein, we report an efficient construction of the lactone bridge of strongylophorine-2, which is a meroditerpenoid isolated from Strongylophora durissima and an inhibitor for HIF-1 transcriptional pathway. Starting from dehydroepiandrosterone acetate, the characteristic lactone has been constructed in 5.4% over 18 steps by employing, (1) modified oxy radical-mediated C–H functionalization at the C24 methyl group, and (2) four-step manipulation of C4 quaternary carbon stereogenic center. The lactone synthesized here is expected as a precursor for (8-desmethyl)strongylophorine-2 which is of particular interest in terms of structure–activity relationships in the inhibition of HIF-1 transcriptional pathway.