Synthesis and evaluation of aminocyclopentitol inhibitors of beta-glucosidases.
[reaction: see text] (1R,2S,3S,4R,5R)-4-Amino-5-(hydroxymethyl)cyclopentane-1,2,3-triol 1, prepared from D-glucose, inhibits beta-glucosidases from Caldocellum saccharolyticum (Ki = 1.8 x 10(-7) M) and from almonds (Ki = 3.4 x 10(-6) M). Inhibition is not influenced by N-ethylation (--> 15) but is strongly reduced upon N-acetylation (--> 12). Inversion of stereochemistry at C(5) (--> 14) has little effect on inhibition of beta-glucosidases. These experiments suggest that 1 acts as an analogue of a protonated beta-glucoside.
Boss
O
O
Department of Chemistry and Biochemistry, University of Bern, Switzerland.
Leroy
E
E
Blaser
A
A
Reymond
J L
JL
D000605:Amino Alcohols / Q000138:chemical synthesis / Q000494:pharmacology*; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D007700:Kinetics; D009754:Nuts / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors*
D000605:Amino Alcohols; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D001617:beta-Glucosidase