Search for alpha-glucosidase inhibitors: new N-substituted valienamine and conduramine F-1 derivatives.
A solid-phase synthesis of new N-substituted valienamines has been developed and new synthesis of (+/-)-conduramine F-1, (-)-conduramine F-1, and (+)-ent-conduramine F-1 is presented, together with the preparation of N-benzylated conduramines F-1. N-Benzylation of both valienamine and (+)-ent-conduramine F-1 improves their inhibitory activity toward alpha-glucosidases significantly. The additional hydroxymethyl group makes valienamine derivatives more active than their (+)-ent-conduramine F-1 analogues.
Łysek
Robert
R
Laboratoire de glycochimie et de synthèse asymétrique, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISIC, BCH, CH-1015 Lausanne-Dorigny, Switzerland.
Schütz
Catherine
C
Favre
Sylvain
S
O'Sullivan
Anthony C
AC
Pillonel
Christian
C
Krülle
Thomas
T
Jung
Pierre M J
PM
Clotet-Codina
Imma
I
Esté
José A
JA
Vogel
Pierre
P
D003511:Cyclohexanols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053138:Cyclohexenes; D003514:Cyclohexylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D006595:Hexosamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C514594:6-aminocyclohex-4-ene-1,2,3-triol; D003511:Cyclohexanols; D053138:Cyclohexenes; D003514:Cyclohexylamines; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D006595:Hexosamines; C030791:valienamine