Preparation of optically activeD‐arylglycines for use as side chains for semisynthetic penicillins and cephalosporins using immobilized subtilisins in two‐phase systems

Abstract

Optically active D-arylglycines, which are of interest for preparation of semisynthetic penicillins and cephalosporins, were isolated from the racemic mixtures of their derivatives using immobilized proteolytic enzyme subtilisin (EC No. 3.4.4. 16). The performance of these reactions in two-phase systems, consisting of water and an immiscible organic solvent, improved the yield, purity, and economics of the process by increasing the substrate solubility and reducing the rate of nonenzymatic hydrolysis. The proportion of the organic phase can be as much as 75% of the overall volume without seriously impairing the enzymatic activity. The optically pure D-and L-arylglycines were liberated from their D- and L-derivatives by acid hydrolysis. The substituent influence of the various arylglycine derivatives on the rate of the enzymatic cleavage reaction was investigated.

Enzymatic resolution of amino acids via ester hydrolysis

“…values of the products were not always given explicitly in the literature, the enantioselectivities shown by this protease were good to excellent. In addition to the examples shown in Scheme 2, optically active Darylglycines were prepared through the enantioselective hydrolysis of their N-protected methyl esters using immobilized subtilisin in two phase systems consisting of water and an immiscible organic solvent (methyl isobutyl ketone or methylene chloride) (Schutt et al, 1985). This procedure increases the substrate solubility and reduces the rate of non-enzymatic hydrolysis, improving the yields and optical purities of the products.…”

Mechanism-based site-directed mutagenesis to shift the optimum pH of the phenylalanine ammonia-lyase from Rhodotorula glutinis JN-1

“…Traditional biocatalytic methods for the production of chiral chemicals have relied on hydrolytic enzymes, such as lipase [5], acylases [15], [28] and hydantoinases [19], and ammonia lyase and aminomutase [9], [13], [23], [31]. Among these enzymes, the phenylalanine ammonia lyase (PAL) (EC 4.3.1.5) and phenylalanine aminomutase (PAM) have been used for the synthesis of a broad range of arylalanines [9], [21], [29], [31].…”

Synthesis of Aryl Glycines by the α Arylation of Weinreb Amides

“…vancomycin)1 and many β‐lactam antibiotics (e.g. penicillins, cephalosporins,2 and nocardicins3). Despite their deceptively simple structure, the enantioselective synthesis of aryl glycines is complicated by the ease of base‐catalyzed racemization of the α stereocenter.…”