1,4-Dihidropiridīna gredzenu saturošu kondensētu heterociklu sintēze un enantiosadalīšana
Date
2012
Authors
Adlere, Ilze
Journal Title
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Publisher
Latvijas Universitāte
Abstract
Sintezētas 1,4-dihidropiridīn-6-merkaptoetiķskābes un 6-metilsulfanil-1,4-dihidropiridīn-3-karbonskābes, pētīta to diastereomēru kristalizācija ar cinhonīnu. Izstrādātas jaunu 1,4-dihidropiridīna gredzenu saturošu kondensētu N,S-heterociklu – 4,7-dihidrotiēno[2,3-b]piridīnu un 5,8-dihidropirido[3,2-e][1,3]tiazīn-2-imīnija hlorīdu kā potenciālo multirezistences modulatoru sintēzes metodes. Pielietojot lipāzi Amano PS un veicot acilēšanu ar vinilacetātu kinētiskās kontroles apstākļos, ar 85% enantiomēro pārākumu iegūts acilētais produkts – 6-aciloksietilsulfanil-1,4-dihidropiridīns un 1,4-dihidropiridīn-
6-merkaptoetanols (98% ee) kā neizreaģējošais substrāts. Enzīmu katalizēta
1,4-dihidropiridīn-6-merkaptoetanola acilēšana ar vinilacetātu ir jauna metode sēra saturošu 1,4-dihidropiridīnu sadalīšanai enantiomēros.
1,4-Dihydropyridine-6-mercaptoacetic acids and 6-methylsulfanyl-1,4-dihydropyridine-3-carboxylic acids were synthesized and crystallization of their diastereomeric cinchonine salts was studied. Synthetic methods for the 1,4-dihydropyridine ring containing condensed N,S-heterocycles – 4,7-dihydrothieno[2,3-b]pyridines and 5,8-dihydro-2H-pyrido [3,2-e][1,3]thiazin-2-iminium chlorides as potential multidrug resistance modulators were developed. By making use of Amano PS lipase as catalyst kinetically controlled acylation with vinyl acetate proceeded with formation of 6-acyloxyethylsulfanyl-1,4-dihydropyridine in 85% enantiomeric excess and 1,4-dihydropyridine-6-mercaptoethanol as unreacted substrate (98% ee). Enzyme catalyzed acylation of 1,4-dihydropyridine-6-mercaptoethanol by making use of vinyl acetate is a new method for enantioseparation of sulfur-containing 1,4-dihydropyridines.
1,4-Dihydropyridine-6-mercaptoacetic acids and 6-methylsulfanyl-1,4-dihydropyridine-3-carboxylic acids were synthesized and crystallization of their diastereomeric cinchonine salts was studied. Synthetic methods for the 1,4-dihydropyridine ring containing condensed N,S-heterocycles – 4,7-dihydrothieno[2,3-b]pyridines and 5,8-dihydro-2H-pyrido [3,2-e][1,3]thiazin-2-iminium chlorides as potential multidrug resistance modulators were developed. By making use of Amano PS lipase as catalyst kinetically controlled acylation with vinyl acetate proceeded with formation of 6-acyloxyethylsulfanyl-1,4-dihydropyridine in 85% enantiomeric excess and 1,4-dihydropyridine-6-mercaptoethanol as unreacted substrate (98% ee). Enzyme catalyzed acylation of 1,4-dihydropyridine-6-mercaptoethanol by making use of vinyl acetate is a new method for enantioseparation of sulfur-containing 1,4-dihydropyridines.
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