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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 stereoiso...

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Autores principales: Usami, Yoshihide, Mizuki, Koji, Kawahata, Rikiya, Shibano, Makio, Sekine, Atsuko, Yoneyama, Hiroki, Harusawa, Shinya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295242/
https://www.ncbi.nlm.nih.gov/pubmed/28124983
http://dx.doi.org/10.3390/md15010022
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author Usami, Yoshihide
Mizuki, Koji
Kawahata, Rikiya
Shibano, Makio
Sekine, Atsuko
Yoneyama, Hiroki
Harusawa, Shinya
author_facet Usami, Yoshihide
Mizuki, Koji
Kawahata, Rikiya
Shibano, Makio
Sekine, Atsuko
Yoneyama, Hiroki
Harusawa, Shinya
author_sort Usami, Yoshihide
collection PubMed
description 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 BF(3)·Et(2)O. 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.
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spelling pubmed-52952422017-02-07 Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors Usami, Yoshihide Mizuki, Koji Kawahata, Rikiya Shibano, Makio Sekine, Atsuko Yoneyama, Hiroki Harusawa, Shinya Mar Drugs Article 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 BF(3)·Et(2)O. 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. MDPI 2017-01-23 /pmc/articles/PMC5295242/ /pubmed/28124983 http://dx.doi.org/10.3390/md15010022 Text en © 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Usami, Yoshihide
Mizuki, Koji
Kawahata, Rikiya
Shibano, Makio
Sekine, Atsuko
Yoneyama, Hiroki
Harusawa, Shinya
Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors
title Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors
title_full Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors
title_fullStr Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors
title_full_unstemmed Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors
title_short Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors
title_sort synthesis of natural o-linked carba-disaccharides, (+)- and (−)-pericosine e, and their analogues as α-glucosidase inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295242/
https://www.ncbi.nlm.nih.gov/pubmed/28124983
http://dx.doi.org/10.3390/md15010022
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