Syntheses and Glycosidase Inhibitory Activities, and in Silico Docking Studies of Pericosine E Analogs Methoxy-Substituted at C6.

Inspired by the significant -glucosidase inhibitory activities of (+)- and (-)-pericosine E, we herein designed and synthesized 16 analogs of these marine natural products bearing a methoxy group instead of a chlorine atom at C6. Four of these compounds exhibited moderate -glucosidase inhibitory activities, which were weaker than those of the corresponding chlorine-containing species. The four compounds could be prepared by coupling reactions utilizing the (-)-pericosine B moiety. An additional in silico docking simulation suggested that the reason of reduced activity of the C6-methoxylated analogs might be an absence of hydrogen bonding between a methoxy group with the surrounding amino acid residues in the active site in -glucosidase.

Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (-)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors.

Pericosine E (6), a metabolite of Periconia byssoides OUPS-N133 was originally isolated from the sea hare Aplysia kurodai, which exists as an enantiomeric mixture in nature. The enantiospecific syntheses of both enantiomers of Periconia byssoides OUPS-N133 has been achieved, along with six stereoisomers, using a common simple synthetic strategy. For these efficient syntheses, highly regio- and steroselective processes for the preparation of bromohydrin and anti-epoxide intermediates were applied. In order to access the unique O-linked carbadisaccharide structure, coupling of chlorohydrin as a donor and anti-epoxide as an acceptor was achieved using catalytic BF3·Et2O. Most of the synthesized compounds exhibited selectively significant inhibitory activity against α-glycosidase derived from yeast. The strongest analog showed almost 50 times the activity of the positive control, deoxynojirimycin.