Long-term continuous production of optically active 2-(4-chlorophenoxy)propanoic acid by yeast lipase in an organic solvent system

Abstract

Long-term continuous optical resolution of 2-(4-chlorophenoxy)propanoic acid was carried out by stereoselective esterification with Celite-adsorbed lipase OF 360 from Candida cylindracea using n-tetradecanol as the second substrate in organic solvent systems. The water content of the Celite-adsorbed lipase affected productivity, 1.0 ~tl water-mg lipase -1 being optimal for preparation of the adsorbed lipase. Watersaturated carbon tetrachloride-isooctane (8:2, v/v) was found to be an excellent organic solvent for the continuous operation. The particle size of Celite had no effect on productivity. Under optimized conditions, the (R)-enantiomer of the acid was continuously esterified with high stereoselectivity in a packed-bed column reactor for 34 days. Furthermore, it was found that treatment of the reactor with acetone made it possible to restore productivity and extend the period of continuous operation for further 29 days.We have demonstrated bioconversion of various lipophilic compounds in organic solvent systems (Sonomoto and Tanaka 1988; Tanaka and Sonomoto 1990), such as the optical resolution of menthol (Koshiro et al. 1985) and 2-(4-chlorophenoxy)propanoic acid (Pan et al. 1990) by stereoselective esterification with lipase. In spite of much work on bioconversion in organic solvents, there have so far been only a few reports on continuous bioconversion (Macrae 1983;Nakanishi et al. 1985Nakanishi et al. , 1988Nakanishi et al. , 1990 and no study on a continuously operated system applying stereoselectivity of biocatalysts.This work deals with long-term continuous production of optically active 2-(4-chlorophenoxy)propanoic acid, the (R)-isomer of which is an important herbicide, by stereoselective esterification with n-tetradecanol by yeast lipase in organic solvents (Fig. 1), and with optimization of the reaction conditions.

Stereoselective bioconversions in continuously operated fixed bed reactors: Modeling and process optimization

“…Furthermore, kinetic resolution has been almost exclusively carried out in batch reactors, although with an increasing demand for chiral synthons the design of appropriate continuous production processes might be commercially advantageous. First results for the application of immobilized lipases in continuously operated fixed bed reactors have been reported for enantioselective esterification (Fukui et al, 1990) and transesterification (Wickli et al, 1992) reactions. In a similar fashion, carrier-adsorbed subtilisin has been used for continuous resolution of racemic amines in organic media (Gutman et al, 1992).…”

Efficient Repeated Use of Alcohol Dehydrogenase with NAD + Regeneration in an Aqueous-organic Two-phase System

“…HLADH is useful for the production of enantiomerically pure biochemical substances (Fukui et al, 1992;Haslegrave and Jones, 1982;Krawczyk and Jones, 1989;Tsuji et al, 1994;Wong et al, 1981). Many immobilization methods for biocatalysts were also reported (Tanaka and Kawamoto, 1999a,b), and many repeated or continuous operation systems have been carried out with immobilized biocatalysts (Chen and Wang, 1991;Fukui et al, 1990Fukui et al, , 1991Xu et al, 1995). In addition to the repeated or continuous use of HLADH, efficient regeneration and repeated or continuous use of this coenzyme is also important for the practical application of HLADH.…”

Synthesis and Biological Activity of Enantiomeric Pairs of Phosphosulfonate Herbicides

“…However, in contrast to our synthetic targets, Mikołajczyk et al primarily H-phosphinates, see the following: Benschop and Van den Berg, 1970;Reiff and Aaron, 1970;Szafraniec et al, 1982), we have explored the possibility of using enzymatic procedures to resolve racemic isopropyl alkyl-(hydroxymethyl)phosphinates 7 and 8. Lipase-mediated acetylation was selected as the most promising transformation because racemic alcohols are considered good substrates for this type of reaction (for recent reviews, see the following: Jones, 1986;Chen and Sih, 1989;Klibanov, 1990;Faber, 1996, Sih et al, 1992Fukui et al, 1990). Lipase-mediated acetylation has proven successful for the resolution of C-chiral (R-hydroxyalkyl)phosphonates (Li and Hammerschmidt, 1993;Khushi et al, 1993); however, in this paper, we describe the first successful lipase-mediated resolution of racemic, Palkyl(hydroxymethyl)phosphinates in which the phosphorus atom is the sole stereogenic center.…”