Synthesis of Dehydro-Dephospho-Fostriecin and Formal Total Synthesis of Fostriecin

Abstract

A formal synthesis of fostriecin (1) and a total synthesis of its related congener dihydro-dephospho-fostriecin 2 have been achieved. The route relies upon the use of the Sharpless dihydroxylation to set the absolute stereochemistry at C-8/9 and Noyori transfer hydrogenation and Leighton allylation to set the C-11 and C-5 relative stereochemistry, respectively. Finally, the divergent functionalization of a C-12/13 alkyne was used to establish the Z,E-dienyne of dehydrodephospho-fostriecin 2 and the Z,Z,E-triene of fostriecin (1).

Strategies for Targeting Serine/Threonine Protein Phosphatases with Small Molecules in Cancer

“…Unfortunately, this study was terminated before reaching the MTD due to instability in storage and unpredictable purity . Nowadays, although the synthesis problem of fostriecin has been solved, the storage stability of fostriecin is still a problem that urgently needs to be addressed. − When combined with carboplatin in ovarian cancer therapy, fostriecin can increase chemosensitivity, DNA damage, and micronuclei formation . The underlying antitumor mechanism includes the regulation of the DDR pathway mediated by PP4 .…”