Effect of Acyl Chain Length and Branching on the Enantioselectivity ofCandidarugosaLipase in the Kinetic Resolution of 4-(2-Difluoromethoxyphenyl)-Substituted 1,4-Dihydropyridine 3,5-Diesters

Abstract

Since 2,6-dimethyl-4-aryl-1,4-dihydropyridine 3,5-diesters themselves are not hydrolyzed by commercially available hydrolases, derivatives with spacers containing a hydrolyzable group were prepared. Seven acyloxymethyl esters of 5-methyl- and 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate were synthesized and subjected to Candida rugosa lipase (CRL) catalyzed hydrolysis in wet diisopropyl ether. A methyl ester at the 5-position and a long or branched acyl chain at C3 gave the highest enantiomeric ratio (E values). The most stereoselective reaction (E = 21) was obtained with 3-[(isobutyryloxy)methyl] 5-methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and this compound was used to prepare both enantiomers of 3-methyl 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate. The absolute configuration of the enzymatically produced carboxylic acid was established to be 4R by X-ray crystallographic analysis of its 1-(R)-phenylethyl amide.

Bis(trimethylsilyl)ketene Acetals as C,O‐Dinucleophiles: One‐Pot Formation of Polycyclic γ‐ and δ‐Lactones from Pyridines and Pyrazines

“…Most of the new structures were assigned through X-ray crystal structure determinations. agents, [12][13][14] such compounds could also be used for the biomimetic reduction of Fischer carbene complexes. [15][16][17] The second was the dinucleophilic addition reactions, since we had discovered that bis(trimethylsilyl)ketene acetals 7 constitute an original class of ketene acetals among nucleophiles, [18][19][20][21] as they can behave as 1,3-carbon,oxygen dinucleophiles 8 in one-pot reactions, as the result of successive cleavage of both oxygen-silicon bonds (Scheme 2).…”

Continuous flow synthesis of β-amino α, β-unsaturated esters in aqueous medium

“…More work on understanding the mass transfer with reaction for different systems and numbering-up approach for producing several hundred kg of the product/day are in progress. solution) and acetic acid (AA) as a catalyst [9] and without any solvent. At room temperature, the reaction for 12 h yielded 82 % product and at 50 ° C, within 60 min, yield was between 93 and 96 % .…”

Electrochemical Biosensor for the Determination of Amlodipine Besylate Based on Gelatin–Polyaniline Iron Oxide Biocomposite Film

“…When the reaction medium was n-butanol/water (10:1), the lipase-catalyzed hydrolysis proceeded with good enantioselectivity. The degradation of diesters was achieved through a two-step reaction (Scheme 1); the first step produced monoacids, and prolongation of the reaction time led to achiral di-acids [41,42]. …”

“…When the reaction medium was n-butanol/water (10:1), the lipase-catalyzed hydrolysis proceeded with good enantioselectivity. The degradation of diesters was achieved through a two-step reaction (Scheme 1); the first step produced monoacids, and prolongation of the reaction time led to achiral di-acids [41,42]. Using t-butyl methyl ether as the solvent in addition to methanol as the nucleophile for Pseudomonas lipase and water as the nucleophile for C. rugosa lipase (CRL), the transformations of 1,4-DHPs were investigated (Scheme 2) [43].…”