Hydrolysis of racemic naproxen methyl

Fig. 27.22 Enantioselective hydrolysis of racemic-Naproxen methyl ester by the encapsulated lipase in the presence of an additive...

Hydrolysis of racemic naproxen methyl ester by C. rugosa lipase [31]. 

The enantioselective hydrolysis of racemic naproxen methyl ester by C. rugosa lipase (CRL) was studied in an aqueous buffer solution/isooctane reaction system in the presence of supercritical CO (Figure 3.21) [31]. The conversion reached 41.3% at 120 bar at 37°C after 2 h of reaction and provided enantiomeric purities of product and substrate of 97.9 and 68.8%, respectively. This corresponded to an enantiomeric ratio (E value) of 193. The lipase remained active for at least 12hat37°C and 120 bar in the supercritical CO medium. 

U. Salgm, S. Salgin, S. Takag, Hydrolysis of racemic naproxen methyl ester by Candida rugosa lipase, I. Supercrit. Fluids 43 (2007) 310-316. 

The racemic resolution of this molecule is very important because the 5 -enantiomer is 28-fold more active than the R-enantiomer. Sakaki and co-workers [4.69] realized the production of (5)-naproxen from the racemic naproxen methyl ester using lipase immobilized in hollow fibers. Their results showed that the MBR had good enzyme stability and enantiomeric excess of up to 0.92. The stereoselective hydrolysis of racemic 2-substituted propionates catalyzed by carboxyl esterase has been performed by Cretich and coworkers... 

Naproxen, (S)-2-(6-methoxy-2-naphthyl)propanoic acid 126 is a nonsteroidal anti-inflammatory and analgesic agent first developed by Syntex [220,221]. Biologically active desired S-naproxen has been prepared by enantioselective hydrolysis of the methyl ester of naproxen by esterase derived from Bacillus subtilis Thai 1-8 [222]. The esterase was subsequently clone in Escherichia coli with over 800-fold ipcrease in activity of enzyme. The resolution of racemic naproxen amide and ketoprofen amides has been demonstrated by amidases from Rhodococcus erythropolis MP50 and Rhodococcus sp. C311 (223-226). 5-Naproxen 126 and 5-ketoprofen 127 (Fig. 44) were obtained in 40% yields (theoretical maximum yield is 50%) and 97% e.e. Recently, the enantioselective esterification of naproxen has been demonstrated using lipase from Candida cylindraceae in isooctane as solvent and trimethylsilyl as alcohol. The undesired isomer of naproxen was esterified leaving desired S isomer unreacted [227]. 

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