A sustainable enzymatic strategy for the preparation of amides by using Candida antarctica lipase B as the biocatalyst and cyclopentyl methyl ether as a green and safe solvent was devised. The method is simple and efficient and it produces amides with excellent conversions and yields without the need for intensive purification steps. The scope of the reaction was extended to the preparation of 28 diverse amides using four different free carboxylic acids and seven primary and secondary amines, including cyclic amines. This enzymatic methodology has the potential to become a green and industrially reliable process for direct amide synthesis.

The enantioselective separation of newly synthesized fluorine-substituted β-phenylalanines has been performed utilizing Cinchona alkaloid-based ion-exchanger chiral stationary phases. Experiments were designed to study the effect of eluent composition, counterion content, and temperature on the chromatographic properties in a systematic manner. Mobile phase systems containing methanol or mixtures of methanol and acetonitrile together with acid and base additives ensured highly efficient enantioseparations. Zwitterionic phases [Chiralpak ZWIX (+) and ZWIX(-)] were found to provide superior performance compared to that by the anion-exchangers (Chiralpak QN-AX and QD-AX). A detailed thermodynamic characterization was also performed by employing van't Hoff analysis. Using typical liquid chromatographic experimental conditions, no marked effect of the flow rate could be observed on the calculated thermodynamic parameters. In contrast, a clear tendency has been revealed about the effect of the eluent composition on the thermodynamics for the zwitterionic phases.

An efficient and novel enzymatic method has been developed for the synthesis of β-fluorophenyl-substituted β-amino acid enantiomers through lipase PSIM (Burkholderia cepasia) catalyzed hydrolysis of racemic β-amino carboxylic ester hydrochloride salts 3a–e in iPr₂O at 45 °C in the presence of Et₃N and H₂O. Adequate analytical methods were developed for the enantio-separation of racemic β-amino carboxylic ester hydrochlorides 3a–e and β-amino acids 2a–e. Preparative-scale resolutions furnished unreacted amino esters (R)-4a–e and product amino acids (S)-5a–e with excellent ee values (≥99%) and good chemical yields (>48%).

Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5–8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino esters were performed in tBuOMe at 65 °C. The unreacted β-amino ester enantiomers (1R,2S) and product β-amino acid enantiomers (1S,2R) were obtained with modest to excellent enantiomeric excess (ee) values (ee_s > 62% and ee_p > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H₂O extraction.

This article provides a review of the paramount lipase-catalyzed strategies employed in the preparation of (2R,3S)-3-amino-2-hydroxy-3-phenylpropionic acid, several of its derivatives, and precursor 2-azetidinones through β-lactam ring opening, OAc hydrolysis, COOEt hydrolysis, O-acylation, and sequential kinetic resolution through a two-step cascade reaction. It involves OAc hydrolysis followed by β-lactam ring opening and β-lactam ring opening followed by hydroxymethyl group degradation of the corresponding racemic compounds, reported over the last 15 years. A brief introduction describes the pharmaceutical and chemical importance of the Taxol molecule as well as various synthetic methods involving its side chain and it delineates the key objectives of this mini-review. The strategies are classified on the basis of reaction types and are presented in chronological order, discussing kinetic and sequential kinetic resolutions in the main text. These reactions yield the intended products, exhibiting excellent enantiomeric excess values.

The present Ph.D. work has been planned to accomplish two major goals. In view of the significance of fluorine-substituted compounds, the first aim was to synthesize a selection of (±)-β-amino carboxylic ester hydrochloride salts 3a–e, then to generate an appropriate lipase-catalyzed method for their resolution through hydrolysis, furnishing enantiopure new β-fluorophenyl-substituted β-amino acids (S)-5a–e and unreacted β-amino esters (R)-4a–e. The second objective of my work was a comparative investigation of different green strategies and then to build an environmentally benign CALB-catalyzed hydrolysis of cis carbocyclic amino esters 6–9.