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Synthesis of Double-Modified Xyloside Analogues for Probing the β4GalT7 Active Site

Willén, Daniel LU ; Bengtsson, Dennis; Clementson, Sebastian; Tykesson, Emil LU ; Manner, Sophie LU and Ellervik, Ulf LU (2018) In Journal of Organic Chemistry 83(3). p.1259-1277
Abstract

Monosubstituted naphthoxylosides have been shown to function as substrates for, and inhibitors of, the enzyme β4GalT7, a key enzyme in the biosynthetic pathway leading to glycosaminoglycans and proteoglycans. In this article, we explore the synthesis of 16 xyloside analogues, modified at two different positions, as well as their function as inhibitors of and/or substrates for the enzyme. Seemingly simple compounds turned out to require complex synthetic pathways. A meta-analysis of the synthetic work shows that, regardless of the abundance of methods available for carbohydrate synthesis, even simple modifications can turn out to be problematic, and double modifications present additional challenges due to conformational, steric, and... (More)

Monosubstituted naphthoxylosides have been shown to function as substrates for, and inhibitors of, the enzyme β4GalT7, a key enzyme in the biosynthetic pathway leading to glycosaminoglycans and proteoglycans. In this article, we explore the synthesis of 16 xyloside analogues, modified at two different positions, as well as their function as inhibitors of and/or substrates for the enzyme. Seemingly simple compounds turned out to require complex synthetic pathways. A meta-analysis of the synthetic work shows that, regardless of the abundance of methods available for carbohydrate synthesis, even simple modifications can turn out to be problematic, and double modifications present additional challenges due to conformational, steric, and stereoelectronic effects.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Organic Chemistry
volume
83
issue
3
pages
19 pages
publisher
The American Chemical Society
external identifiers
  • scopus:85041624906
ISSN
0022-3263
DOI
10.1021/acs.joc.7b02809
language
English
LU publication?
yes
id
5c2bd194-d347-4ec8-a1e8-65dc59e60feb
date added to LUP
2018-02-21 10:07:50
date last changed
2018-05-29 09:52:28
@article{5c2bd194-d347-4ec8-a1e8-65dc59e60feb,
  abstract     = {<p>Monosubstituted naphthoxylosides have been shown to function as substrates for, and inhibitors of, the enzyme β4GalT7, a key enzyme in the biosynthetic pathway leading to glycosaminoglycans and proteoglycans. In this article, we explore the synthesis of 16 xyloside analogues, modified at two different positions, as well as their function as inhibitors of and/or substrates for the enzyme. Seemingly simple compounds turned out to require complex synthetic pathways. A meta-analysis of the synthetic work shows that, regardless of the abundance of methods available for carbohydrate synthesis, even simple modifications can turn out to be problematic, and double modifications present additional challenges due to conformational, steric, and stereoelectronic effects.</p>},
  author       = {Willén, Daniel and Bengtsson, Dennis and Clementson, Sebastian and Tykesson, Emil and Manner, Sophie and Ellervik, Ulf},
  issn         = {0022-3263},
  language     = {eng},
  month        = {02},
  number       = {3},
  pages        = {1259--1277},
  publisher    = {The American Chemical Society},
  series       = {Journal of Organic Chemistry},
  title        = {Synthesis of Double-Modified Xyloside Analogues for Probing the β4GalT7 Active Site},
  url          = {http://dx.doi.org/10.1021/acs.joc.7b02809},
  volume       = {83},
  year         = {2018},
}