Activation of pig liver esterase in organic media with organic polymers: application to the enantioselective acylation of racemic functionalized secondary alcohols.
Pig liver esterase (PLE) shows practically no activity in acylation of alcohols with vinylic esters in organic solvents. However, addition of methoxypoly(ethylene glycol) (MPEG), bovine serum albumin (BSA), TentaGelAmino resin (TGA), or aminomethyl polystyrene (AMPS) confers activity to PLE in acylation of alcohols with vinyl propionate in organic solvents of low water content. Polymer-activated PLE showed high enantioselectivities (E > 100) in the acylation of racemic 1-alkoxy-, 1-ethylsulfanyl-, and 1-fluoro-3-aryl-2-propanols as well as racemic 1-phenoxy-2-propanol and racemic 1-methoxy-2-phenoxy-2-propanol. The synthetic utility of polymer-activated PLE has been demonstrated by the gram-scale resolution of 1-methoxy-3-phenyl-2-propanol, 1-ethylsulfanyl-3-phenyl-2-propanol, 1-methoxy-3-p-methoxyphenyl-2-propanol, 1-fluoro-3-phenyl-2-propanol, and 1-methoxy-3-phenoxy-2-propanol. In PLE-catalyzed acylation of alcohols with vinyl propionate, acetaldehyde and propionic acids, both being detrimental to the enzyme, are formed as byproducts. In addition, the water content of the system, which is critical for the activity of pig liver esterase, is lowered because of a competing enzymatic hydrolysis of the acyl donor. The polymers TGA, BSA, and AMPS not only scavenge the aldehyde and the acid through imine formation and neutralization, respectively, but replenish at least in part also the water consumed in the competing hydrolysis of the acyl donor. A recovery of PLE together with the polymer was achieved without major loss of activity through their immobilization on a water-saturated polyaramide membrane, which occurs spontaneously in organic solvents.
Gais
H J
HJ
Institut für Organische Chemie der Rheinisch-Westfälischen Technischen Hochschule Aachen, Professor-Pirlet-Strasse 1, D-52056 Aachen, Germany. Gais@RWTH-Aachen.de
Jungen
M
M
Jadhav
V
V
D000215:Acylation; D000438:Alcohols / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004950:Esterases / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D012997:Solvents / Q000494:pharmacology*; D013237:Stereoisomerism; D013552:Swine; D013696:Temperature
D000438:Alcohols; D011108:Polymers; D012997:Solvents; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D004950:Esterases