From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar: Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase

Dan Lu, Sha Zhu, Lukasz F. Sobala, Ganeko Bernardo-Seisdedos, Oscar Millet, Yongmin Zhang, Jesus Jiménez-Barbero, Gideon J. Davies, Matthieu Sollogoub*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Understanding the enzyme reaction mechanism can lead to the design of enzyme inhibitors. A Claisen rearrangement was used to allow conversion of an α-1,4-disaccharide into an α-1,3-linked glycosyl carbasugar to target the endo-α-mannosidase from the GH99 glycosidase family, which, unusually, is believed to act through a 1,2-anhydrosugar "epoxide" intermediate. Using NMR and X-ray crystallography, it is shown that glucosyl carbasugar α-aziridines can act as reasonably potent endo-α-mannosidase inhibitors, likely by virtue of their shape mimicry and the interactions of the aziridine nitrogen with the conserved catalytic acid/base of the enzyme active site.

Original languageEnglish
Pages (from-to)7488-7492
Number of pages5
JournalOrganic Letters
Issue number23
Early online date14 Nov 2018
Publication statusPublished - 7 Dec 2018

Bibliographical note

© 2018 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

Cite this