Elemér Fogassy

A quantitative approach to optical resolution

Abstract Significant statistical relationships have been found between the parameters characterizing the results and circumstances of the resolutions of seventeen phenylglycine derivatives. The successful predictions given for the results of six independent resolutions prove the utility of these relationships.

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.

Study of the diastereoisomers formed between (N-alkyl)-pipecolic acid-anilides and 2R,3R-tartaric acid or O,O′-dibenzoyl-2R,3R-tartaric acid. Do the tartaric acids form molecular-complexes, instead of salts during optical resolutions?

It was found that during the optical resolution of (N-alkyl)-pipecolic acid-anilides by 2R,3R- tartaric acid and O,O′-dibenzoyl-2R,3R-tartaric acid that the precipitated diastereoisomer was not the salt but a diastereoisomeric complex in 8 cases from 13. The results indicate that tartaric acids may be used as general resolving agents for optical resolution of racemates even having no basic group.

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.

Molecular chiral recognition in supercritical solvents

Abstract The intensity of molecular chiral interactions resulting in differences between physical and chemical properties of diastereomeric molecules is solvent dependent. This difference makes it possible to separate the enantiomers of a given substance by using chiral agents. A solvent of supercritical state was involved to study its influence on molecular chiral recognition. It was observed that the differences between the diastereomers in supercritical CO 2 are so big compared to traditional solvents that a novel, more efficient method for optical resolution can be developed, employing a variety of resolution agents in a much wider range than it was previously assumed.

Separation of non-racemic mixtures of enantiomers: an essential part of optical resolution

Non-racemic enantiomeric mixtures form homochiral and heterochiral aggregates in melt or suspension, during adsorption or recrystallization, and these diastereomeric associations determine the distribution of the enantiomers between the solid and other (liquid or vapour) phases. That distribution depends on the stability order of the homo- and heterochiral aggregates (conglomerate or racemate formation). Therefore, there is a correlation between the binary melting point phase diagrams and the experimental ee(I)vs. ee(0) curves (ee(I) refers to the crystallized enantiomeric mixtures, ee(0) is the composition of the starting ones). Accordingly, distribution of the enantiomeric mixtures between two phases is characteristic and usually significant enrichment can be achieved. There are two exceptions: no enrichment could be observed under thermodynamically controlled conditions when the starting enantiomer composition corresponded to the eutectic composition, or when the method used was unsuitable for separation. In several cases, when kinetic control governed the crystallization, the character of the ee(0)-ee(I) curve did not correlate with the melting point binary phase diagram.

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.

Supercritical fluid extraction: A novel method for the resolution of tetramisole

Abstract A new resolution method, based on the selective distribution of enantiomers between a chiral solid and an achiral supercritical fluid phase, is reported. The chiral solid phase is formed from the optically active dicarboxylic acid derivative, (2 R ,3 R )- O , O ′-dibenzoyltartaric acid, and the racemic base (tetramisole). A new method is also described for the enrichment of enantiomeric mixtures which have an enantiomeric ratio other than 1:1. This is based on the partial salt formation of the enantiomeric mixture with an achiral substance, which is then followed by supercritical fluid extraction of the free enantiomer. The extract has an enantiomeric composition which is different from the starting mixture. The method is applied to an enantiomeric mixture of tetramisole with hydrochloric acid.

A convenient method for optical resolutions via diastereoisomeric salt formation

Abstract With the advantage of the method using two immiscrible solvents and half - equivalent amount of the resolving agent, higher optical purity can be obtained than in cases of any other resolution via diastereoisomeric salt formation, besides it is a faster procedure for resolution of a new racemate as well.

Predictions of which diastereoisomeric salt precipitates during an optical resolution via diastereoisomeric salt formation

Abstract The DSC data of sixteen conglomerate forming diastereoisomeric salt pairs were analysed. It was demonstrated that during optical resolution via fractional crystallization of diastereoisomeric salt pairs always that diastereoisomeric salt precipitates which has the higher melting point. When one of the salts is amorphous that remains in the mother liquor. If one of the diastereoisomeric salt crystallizes with solvate that will precipitate during optical resolutions.