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Total Syntheses of Casuarine and Its 6‐ O ‐α‐Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families
Author(s) -
Cardona Francesca,
Parmeggiani Camilla,
Faggi Enrico,
Bonaccini Claudia,
Gratteri Paola,
Sim Lyann,
Gloster Tracey M.,
Roberts Shirley,
Davies Gideon J.,
Rose David R.,
Goti Andrea
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200801578
Subject(s) - glucoside , glycoside hydrolase , trehalase , stereochemistry , enzyme , stereoselectivity , chemistry , cycloaddition , glycoside , nitrone , biochemistry , catalysis , medicine , alternative medicine , pathology
Abstract Selective glucosylation : Total synthesis of naturally occurring casuarine ( 1 ) and the first total synthesis of casuarine 6‐ O ‐α‐glucoside ( 2 ) were achieved through complete stereoselective nitrone cycloaddition, Tamao–Fleming oxidation and selective α‐glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes.Total synthesis of naturally occurring casuarine ( 1 ) and the first total synthesis of casuarine 6‐ O ‐α‐glucoside ( 2 ) were achieved through complete stereoselective nitrone cycloaddition, Tamao–Fleming oxidation and selective α‐glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.