Biocatalytic synthesis of some chiral pharmaceutical intermediates by lipases

Abstract

Chiral intermediates were prepared by biocatalytic processes for the chemical synthesis of three pharmaceutical drug candidates. These include (i) the synthesis of [(3R‐cis)‐3‐(acetyloxy)‐4‐phenyl‐2‐azetidinone2 for the semi‐synthesis of paclitaxel (taxol)5, an anticancer compound; (ii) synthesis of chiral (exo,exo)‐7‐oxabicyclo [2.2.1] heptane‐2,3‐dimenthanol monoacetate ester9 for the chemoenzymatic preparation of a thromboxane A2 antagonist; (iii) the enzymatic synthesis ofS‐(−) 3‐benzylthio‐2‐methylpropanoic acid, a key chiral intermediate for the synthesis of antihypertensive drugs captopril10 or zofenopril13.

Lipase-catalyzed kinetic resolution of 2-methylene-substituted cycloalkanols in batch and continuous-flow modes

“…A continuous packed-bed reactor offers the following advantages over a batch reactor: easy, automatic control and operation, reduction of labor costs, better control of operating conditions and products [18,19]. There are only a few examples of hydrolase-catalyzed enantioselective processes carried out in continuous-flow systems [20][21][22]. Most of these studies were aimed at the biocatalytic syntheses of chiral pharmaceutical intermediates and were performed on a relatively large scale using immobilized lipases in a packed-bed reactor [20,23].…”

“…There are only a few examples of hydrolase-catalyzed enantioselective processes carried out in continuous-flow systems [20][21][22]. Most of these studies were aimed at the biocatalytic syntheses of chiral pharmaceutical intermediates and were performed on a relatively large scale using immobilized lipases in a packed-bed reactor [20,23]. It was found that stainless steel continuous-flow packed-bed bioreactors could be effectively used to study the effects of temperature, pressure and flow rate on stereoselective biotransformations, such as lipasecatalyzed kinetic resolution [24].…”

Immobilization of lipase from Candida rugosa on Sepabeads®: the effect of lipase oxidation by periodates

“…They are resistant to solvents and are exploited in a broad spectrum of biotechnological applications [3]. Novel biotechnological applications, such as biopolymer synthesis [4], biodiesel production [5][6][7], treatment of fat-containing waste effluents [8], enantiopure synthesis of pharmaceuticals [9,10] and nutraceutical agents [11], have been established successfully.…”

Novel Sol‐Gel Lipases by Designed Bioimprinting for Continuous‐Flow Kinetic Resolutions

“…[11][12][13] Most of the continuousmode biocatalytic syntheses of chiral pharmaceutical intermediates are performed on a relatively large scale using immobilized lipases in a packed-bed reactor. [13,14] Recently, continuous-flow packed-bed bioreactors were used to study the effects of tempera-ture, pressure and flow rate on lipase-catalyzed kinetic resolutions. [15,16] The catalytic activity, selectivity, specificity and enzyme stability are key factors affecting the efficiency of biocatalysts.…”