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Synthesis and Glycosidase Inhibition Studies of 5‐Methyl‐Substituted Tetrahydroxyindolizidines and ‐pyrrolizidines Related to Natural Hyacinthacines B
Author(s) -
Martella Daniele,
Cardona Francesca,
Parmeggiani Camilla,
Franco Francisco,
Tamayo Juan A.,
Robina Inmaculada,
MorenoClavijo Elena,
MorenoVargas Antonio J.,
Goti Andrea
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300103
Subject(s) - chemistry , stereoselectivity , allylic rearrangement , stereochemistry , glycoside hydrolase , selectivity , enzyme , amylase , combinatorial chemistry , organic chemistry , catalysis
The synthesis of three tetrahydroxyindolizidines and one tetrahydroxypyrrolizidine related to natural hyacinthacines B and their biological evaluation as glycosidase inhibitors is reported. The target molecules were obtained through highly stereoselective cycloadditions between sugriched allylic and homoallylic alcohols. This allowed the installation of a methyl group at C5 – a common feature of many natural hyacinthacines – with high control over the stereoselectivity. The new compounds inhibit amyloglucosidase from Aspergillus niger and β‐glucosidase from almonds. Compound 1 is a competitive inhibitor of amyloglucosidase and shows a fair selectivity towards this enzyme. The presence of C5‐Me substitution in indolizidines 2 and 3 slightly diminishes the inhibitory activity towards amyloglucosidase whereas it improves the inhibitory properties towards β‐glucosidase.