Facile and Efficient Synthesis of Naturally Occurring Carbasugars (+)-Pericosines A and C

Abstract

An efficient synthesis of antitumor marine natural product (+)-pericosine A was achieved from (-)-quinic acid in 11.7% overall yield, which is 20 times better than our previously reported synthesis. The crucial steps of this synthesis include the regio- and stereoselective bromohydrination of an unstable diene and the ring opening of an epoxide. This synthetic route was applicable to a synthesis of (+)-pericosine C and also to a synthesis of (-)-pericosine C.

Divergent Synthesis and Evaluation of Inhibitory Activities against Cyclooxygenases-1 and -2 of Natural Withasomnines and Analogues

“…24) Because of these interesting biological activities, several reports of the synthesis of 1a were disclosed. [27][28][29][30][31][32][33][34][35][36] In the course of our synthetic studies of small natural products and their analogues, [37][38][39][40][41][42] we recently reported the divergent synthesis of withasomnines 1a-c and their analogues via 4-hydroxypyrazole intermediates in a preliminary communication. 43) We herein describe the details of the divergent synthesis of natural 1a-c as well as nine withasomnine analogues 1d-l, which were easily prepared by the Suzuki-Miyaura coupling of key intermediate 16.…”

Synthesis of Marine-Derived Carbasugar Pericosines

“…The results implied that this was a plausible precursor for pericosines via a biosynthetic pathway. This speculation was applied to the second-generation synthesis of 1 [98]. The key reactions in this new simpler and more effective synthetic avenue to (þ)-1 were the regio-and stereoselective bromohydrination of an unstable diene and the regio-and stereoselective ring opening of epoxide 81.…”

The Medicinal Value of Biodiversity: New Hits to Fight Cancer

“…Among the members of this family of carbasugars, pericosine A is the most important, because it was reported to possess significant inhibitory activity against protein kinase EGFR (epidermal growth factor receptor) and human topoisomerase II, in addition to its antitumor activity against P388 lymphocytic leukemia cell line in vitro and in vivo (Numata et al, 1997;Yamada et al, 2007). Various reports in literature have shown the efforts of researchers to characterize the structure of pericosine molecules and develop new routes for their synthesis (Usami et al, 2009). Since 1941, when penicillin was introduced in the market, secondary metabolites of bacteria have been studied as promising drug candidates for the treatment of diverse pathologies, including cancer.…”