New enzymatic strategies for the preparation of pharmaceutically important enantiomeric β-amino acid derivatives

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

A Sustainable Green Enzymatic Method for Amide Bond Formation

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

Synthesis of new fluorine-containing β-amino acid enantiomers through lipase catalyzed hydrolysis

An efficient and novel enzymatic method was developed for the synthesis of β-aryl-fluorinecontaining β-amino acid enantiomers through lipase PS IM (Burkholderia cepasia) catalyzed hydrolysis in i-Pr2O at 45 °C in the presence of Et3N. In order to follow the enzymatic reactions, an adequate analytical method was devised for the enantioseparation of racemic βamino esters and β-amino acids

Green Strategies for the Preparation of Enantiomeric 5–8-Membered Carbocyclic β-Amino Acid Derivatives through CALB-Catalyzed Hydrolysis

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 (ees > 62% and eep > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H2O extraction