Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

In this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten–Baumann acylation or by coupling employing HATU a...

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Main Authors:	Joana Salta, Jens Dernedde, Hans-Ulrich Reissig
Format:	Article
Language:	English
Published:	Beilstein-Institut 2015-05-01
Series:	Beilstein Journal of Organic Chemistry
Subjects:	aminopolyols carbohydrate mimetics carboxylic acid amides inhibition multivalency selectins sulfation
Online Access:	https://doi.org/10.3762/bjoc.11.72

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spelling	doaj-0f0f961874804170816d23dc148c243e2021-02-02T01:03:05ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972015-05-0111163864610.3762/bjoc.11.721860-5397-11-72Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitorsJoana Salta0Jens Dernedde1Hans-Ulrich Reissig2Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, D-14195 Berlin, GermanyCharité Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Campus Virchow Klinikum, Augustenburger Platz 1, D-13353 Berlin, GermanyFreie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, D-14195 Berlin, GermanyIn this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten–Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz 1H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the compounds could not be tested as L-selectin inhibitor by SPR due to their insolubility in water, nevertheless, a divalent and a trivalent amide showed surprisingly good activities with IC50 values in the low micromolar range.https://doi.org/10.3762/bjoc.11.72aminopolyolscarbohydrate mimeticscarboxylic acid amidesinhibitionmultivalencyselectinssulfation
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Joana Salta Jens Dernedde Hans-Ulrich Reissig
spellingShingle	Joana Salta Jens Dernedde Hans-Ulrich Reissig Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors Beilstein Journal of Organic Chemistry aminopolyols carbohydrate mimetics carboxylic acid amides inhibition multivalency selectins sulfation
author_facet	Joana Salta Jens Dernedde Hans-Ulrich Reissig
author_sort	Joana Salta
title	Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors
title_short	Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors
title_full	Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors
title_fullStr	Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors
title_full_unstemmed	Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors
title_sort	synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as l-selectin inhibitors
publisher	Beilstein-Institut
series	Beilstein Journal of Organic Chemistry
issn	1860-5397
publishDate	2015-05-01
description	In this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten–Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz 1H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the compounds could not be tested as L-selectin inhibitor by SPR due to their insolubility in water, nevertheless, a divalent and a trivalent amide showed surprisingly good activities with IC50 values in the low micromolar range.
topic	aminopolyols carbohydrate mimetics carboxylic acid amides inhibition multivalency selectins sulfation
url	https://doi.org/10.3762/bjoc.11.72
work_keys_str_mv	AT joanasalta synthesisofmultivalentcarbohydratemimeticswithaminopolyolendgroupsandtheirevaluationaslselectininhibitors AT jensdernedde synthesisofmultivalentcarbohydratemimeticswithaminopolyolendgroupsandtheirevaluationaslselectininhibitors AT hansulrichreissig synthesisofmultivalentcarbohydratemimeticswithaminopolyolendgroupsandtheirevaluationaslselectininhibitors
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Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

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