title: Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (-)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors.
abstract: Pericosine E (6), a metabolite ofPericonia byssoidesOUPS-N133 was originally isolated from the sea hareAplysia kurodai, which exists as an enantiomeric mixture in nature. The enantiospecific syntheses of both enantiomers ofPericonia byssoidesOUPS-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 andanti-epoxide intermediates were applied. In order to access the uniqueO-linked carbadisaccharide structure, coupling of chlorohydrin as a donor andanti-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.
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan. usami@gly.oups.ac.jp.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Usami
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan. d12007@gly.oups.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Mizuki
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan. katahaba4@icloud.com.
authors.forename: Rikiya
authors.initials: R
authors.lastname: Kawahata
authors.affiliation: Laboratory of Pharmacognosy, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan. shibano@gly.oups.ac.jp.
authors.forename: Makio
authors.initials: M
authors.lastname: Shibano
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan. SekineA@mbox.pref.osaka.lg.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan. yoneyama@gly.oups.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoneyama
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan. harusawa@gly.oups.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Harusawa
mesh_terms: D017485:1-Deoxynojirimycin / Q000737:chemistry; D000438:Alcohols / Q000737:chemistry; D001203:Ascomycota / Q000737:chemistry; D002728:Chlorohydrins / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry*; D012765:Shikimic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D015003:Yeasts / Q000737:chemistry; D000520:alpha-Glucosidases / Q000737:chemistry*
chemical_list: D000438:Alcohols; D002728:Chlorohydrins; D004187:Disaccharides; D004852:Epoxy Compounds; D065089:Glycoside Hydrolase Inhibitors; C023963:bromohydrins; C501633:deoxynojirimycine; C000596831:pericosine E; D017485:1-Deoxynojirimycin; D012765:Shikimic Acid; D000520:alpha-Glucosidases; D005944:Glucosamine
keywords: O-linked carba-disaccharide; enantiomeric mixture; marine natural product; pericosine E; synthesis; α-glucosidase inhibitor