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

Marine Drugs

Atsuko Sekine¹  Koji Mizuki¹  Hiroki Yoneyama¹  Yoshihide Usami¹  Shinya Harusawa¹  Rikiya Kawahata¹  Makio Shibano² 

[1] Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan;Laboratory of Pharmacognosy, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan;

关键词: synthesis;    pericosine E;    marine natural product;    O-linked carba-disaccharide;    α-glucosidase inhibitor;    enantiomeric mixture;   

DOI  :  10.3390/md15010022

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown