Usami Yoshihide, Mizuki Koji, Kawahata Rikiya, Shibano Makio, Sekine Atsuko, Yoneyama Hiroki, Harusawa Shinya
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.
Mar Drugs. 2017 Jan 23;15(1):22. doi: 10.3390/md15010022.
Pericosine E (), a metabolite of OUPS-N133 was originally isolated from the sea hare , which exists as an enantiomeric mixture in nature. The enantiospecific syntheses of both enantiomers of 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 -epoxide intermediates were applied. In order to access the unique -linked carbadisaccharide structure, coupling of chlorohydrin as a donor and -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.
Pericosine E（）是OUPS-N133的一种代谢产物，最初从海兔中分离得到，在自然界中它以对映体混合物的形式存在。使用一种常见的简单合成策略，已经实现了OUPS-N133两种对映体以及六种立体异构体的对映体特异性合成。对于这些高效合成，应用了制备溴醇和环氧中间体的高度区域和立体选择性过程。为了获得独特的β-连接碳二糖结构，使用催化量的BF₃·Et₂O实现了氯醇作为供体与环氧作为受体的偶联。大多数合成化合物对源自酵母的α-糖苷酶表现出选择性显著的抑制活性。最强的类似物显示出几乎是阳性对照脱氧野尻霉素活性的50倍。
