Asymmetric synthesis of 3-amino-4-hydroxy-2-(hydroxymethyl)pyrrolidines as potential glycosidase inhibitors.
Three diastereoisomers of 3-amino-4-hydroxy-2-(hydroxymethyl)pyrrolidine have been synthesised by a divergent route starting from trans-4-hydroxy-L-proline. Regio- and stereoselective introduction of the 3-amino and 4-hydroxyl functional groups was achieved using either a tethered aminohydroxylation reaction or by employing intra- and intermolecular epoxide-opening strategies. Preliminary biological data indicate that two of these novel amino pyrrolidines are moderate inhibitors of beta-galactosidase.
Curtis
Kim L
KL
Department of Chemistry, University of Leicester, Leicester, UK LE1 7RH.
Evinson
Emma L
EL
Handa
Sandeep
S
Singh
Kuldip
K
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006900:Hydroxylation; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D000519:alpha-Galactosidase / Q000037:antagonists & inhibitors / Q000737:chemistry; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors / Q000737:chemistry
D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D006026:Glycoside Hydrolases; D000519:alpha-Galactosidase; D001616:beta-Galactosidase