Intramolecular reductive cyclization strategy to the synthesis of (-)-6-methyl-3-hydroxy-piperidine-2-carboxylic acid, (+)-6-methyl-(2-hydroxymethyl)-piperidine-3-ol and their glycosidase inhibitory activity.
The first stereoselective synthesis of (2S,3R,6S)-6-methyl-3-hydroxy-piperidine-2-carboxylic acid (-)-6 and (2R,3R,6S)-6-methyl-(2-hydroxymethyl)-piperidine-3-ol (+)-7 was achieved starting from readily available d-glucose in 14 steps with 17% overall yield for both the compounds. The key feature of the present strategy includes the Wittig-olefination for the preparation of required conjugated keto-azide 9 and construction of 2,3,6-trisubstituted piperidine skeleton 11 by applying intramolecular reductive cyclization of conjugated keto-azide intermediate. The glycosidase inhibitory activity of compounds 6 and 7 towards several glycosidases has been evaluated.
Garware Research Centre, Department of Chemistry, University of Pune, Pune 411007, India.
Vishwas U
VU
Pawar
Sanjay T
ST
Chavan
Sushma G
SG
Sabharwal
Vaishali S
VS
Shinde
D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056506:Geobacillus / Q000201:enzymology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013237:Stereoisomerism
C555998:6-methyl-3-hydroxypiperidine-2-carboxylic acid; D004791:Enzyme Inhibitors; D010875:Pipecolic Acids; D010880:Piperidines; C032727:piperidine; D006026:Glycoside Hydrolases