József Bálint

Optical Resolution of Racemic Alcohols via Diastereoisomeric Supramolecular Compound Formation with O,O′-Dibenzoyl-(2R,3R)-tartaric Acid

Abstract O , O ′-Dibenzoyl-(2 R ,3 R )-tartaric acid (DBTA) forms a hydrogen bonded supramolecular compound with alcohols. The supramolecular compound formation is enantioselective for a large number of chiral alcohols, therefore DBTA can be used as resolving agent, also for compounds having no basic group. The condition of the complex formation is that the guest molecule should contain a proton donating group and a fitting aliphatic chain or cycloalkane ring.

Baker's yeast mediated stereoselective biotransformation of 1-acetoxy-3-aryloxypropan-2-ones

Abstract A series of 1-acetoxy-3-aryloxypropan-2-ones 1a–m were synthesized and subjected to biotransformation by bakers yeast yielding optically active monoacetates 5 or ent - 5 and/or diols 4 of moderate to excellent enantiomeric purity. The dependence of the reduction/hydrolysis ratio and stereoselectivity on the size and substitution pattern of the aromatic moiety in the substrate is also discussed.

Synthesis, absolute configuration and intermediates of 9-fluoro- 6,7- dihydro-5-methyl-1-oxo-1H,5H-benzo[i.j]quinolizine-2-carboxylic acid (flumequine)

Abstract The antibacterial agent 9-fluoro-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid (flumequine) was synthesized in optically active form from 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ). Racemic FTHQ was resolved with the enantiomers of 3-bromocamphor-8-sulfonic acid. The configurations were established by X-ray structures of the two diastereoisomeric salts. Enantiomeric excesses were determined by 1H NMR analysis.

Baker's yeast mediated reduction of dihydroxyacetone derivatives

Several monoprotected dihydroxyacetone derivatives 4a‐d and their acetates 5a‐d were prepared and subjected to biotransformation with baker’s yeast. The simple chemical modification of the substrates (i.e. transforming the relatively small hydrophilic hydroxymethyl group into a larger hydrophobic acetoxymethyl moiety) inverted the sense of enantiotope selectivity of these reductions yielding optically active diols 6a‐d, or their enantiomeric acetates (7a‐d) and diols (ent-6a‐d), respectively.

Unusual phenomena during the resolution of 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ): Thermodynamic-kinetic control

Abstract 6-Fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ) was resolved in several different solvents by tartaric acid derivatives as the most common acidic resolving agents available in industrial quantities. Strong reaction kinetics and solvent dependence were observed, curiously without solvation. In possession of these findings, an economic resolution process is proposed, which is completed by the incorporation of a racemization step.

Resolution of α-phenylethylamine by its acidic derivatives

Abstract α-Phenylethylamine was resolved by its own derivatives formed with a homologous series of dicarboxylic acids. The structure of the oxalamic acid diastereoisomeric salts was investigated by the single-crystal X-ray diffraction method.

Resolution of the flumequine intermediate 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline

Abstract Racemic 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ) was resolved by the N -phthaloyl derivative of the ( R )-enantiomer. The enantiomeric mixture was very effectively enriched by recrystallisation from either the melt (working best for mixtures of relatively high starting enantiomeric purities) or from solution of its hydrochloride salt (giving good results when applied for mixtures of moderate to medium enantiomeric purities).

Lipase-catalyzed enantiotope selective acetylation of 2-acyloxypropane-1,3-diols. Influence of the acyl moiety on the selectivity

Abstract Preparation and lipase-catalyzed enantiotope selective acetylation of the prochiral 2-acyloxypropane-1,3-diols (1a–h) including sulfonic ester (1a–c) and carboxylic ester (1d–h) series is described. A strong influence of the acyl moiety in these diols on the enantiotope selectivity of the porcine pancreatic lipase (PPL)-catalyzed reaction with vinyl acetate was observed. The best results were achieved with the 2-(4-methylbenzoyl)oxy- and cyclohexanecarbonyloxypropane-1,3-diols (1g and 1h) resulting in acetylated products (2g) of ≥98% e.e. in 77% yield and (2h) of 95% e.e. in 66% yield, respectively.

ISOMER AND ENANTIOMER SEPARATION OF 2- AND 4-ALKYL-CYCLOHEXANOLS BY STEREOSELECTIVE COMPLEX FORMATION WITH O,O′-DIBENZOYL- (2R,3R)-TARTARIC ACID

Stereoisomeric mixtures of 2- and 4-alkyl-cyclohexanols form complex with O,O′-dibenzoyl-(2R,3R)-tartaric acid. The diastereoisomer complex formation can be used for isomer and enatiomer separation as it is trans- and enantioselective in the case of 2-alkyl-cyclohexanols and trans-selective in the case of 4-alkyl-cyclohexanols.

Optical resolution of 1-(1-naphthyl)ethylamine by its dicarboxylic acid derivatives: Structural features of the oxalic acid derivative diastereomeric salt pair

Optical resolution methods were established for racemic 1-(1-naphthyl) ethylamine. The resolving agents were synthesized by N-derivatizing (R)-1-(1-naphthyl) ethylamine with dicarboxylic acids. Oxalic, malonic, and succinic acid derivatives were found to be suitable resolving agents. These resolutions are parallel to a series of optical resolutions of 1-phenylethylamine which had been previously performed by our research group using similar derivative resolving agents (Balint et al., Tetrahedron: Asymmetry 2001;12:1511-1518.) The comparison of the results of the enantiomer separations is performed. The diastereomeric salts formed with (R)-N-[1-(1-naphthyl)ethyl]oxalamic acid were investigated by single crystal X-ray diffraction. The crystal structures were compared with the previously published structures of the diastereomers of the phenyl-substituted analogue, namely (R)- and (S)-1-phenylethylammonium (R)-N-(1-phenylethyl)oxalamates (Balint et al., Tetrahedron: Asymmetry 2001;12:1511-1518).