Glycidic acid methyl ester

An example of an industrial membrane bioreactor is the hollow-fiber membrane system for the production of (-)-MPGM (3-(4-methoxyphenyl)glycidic acid methyl ester), which is an important intermediate for the production of diltiazem hydrochloride [81, 82]. For the enantiospecific hydrolysis of MPGM a hollow-fiber ultrafiltration membrane with immobilized lipase from Serratia marcescens is used. (-f)-MPGM is selectively converted into (2S,3J )-(-F)-3-(4-methoxyphenyl)glyci-dic acid and methanol. The reactant is dissolved in toluene, whereas the hydrophilic product is removed via the aqueous phase at the permeate side of the membrane, see Fig. 13.9. EnantiomericaUy pure (-)-MPGM is obtained from the to-... 

MPGM=/)-methoxyphenyl-glycidic acid methyl ester... 

This knowledge was applied for even more complicated, bifunctional compounds such as phenyl glycidic acid methyl ester 3 to yield alpha-ketone carboxylic acid esters 4 such as 3-phenylpyroracemic acid methylesters (Eq. 15.2.2). 

Fig. 15.2 Catalyst screening for the conversion of phenyl glycidic acid methyl ester to 3-phenylpyroracemic acid methylester...

An immobilized lipase, from M. miehei, was used by Aaltonen s group for the kinetic resolution of tra w-3-(4-methoxyphenyl)glycidic acid methyl ester [Eq. (13)], a precursor in the preparation of the calcium antagonist drug diltiazem (91) ... 

Trans-(2R,3S)-(4-methoxyphenyl)glycidic acid methyl ester is an intermediate in the synthesis of diltiazem, a coronary vasodilator and a calcium channel blocker with... 

The lipase from Serratia marcescens has a high enantioselectivity (E = 135) for the (2R,3S)-(4-methoxyphenyl) glycidic acid methyl ester, which acts as a competitive inhibitor. The formed acid (hydrolyzed (+)-methoxyphenylglycidate) is unstable and decarboxylates to give 4-methoxyphenylacetaldehyde this aldehyde strongly inhibits and deactivates the enzyme. It is removed by transfer to the aqueous phase by formation of a water-soluble adduct with sodium hydrogen sulfite added to the aqueous phase. The bisulfite acts also as a buffer to maintain constant pH during synthesis. 

The enantioselective hydrolysis is carried out in an organic-aqueous two-phase reactor (toluene/water), where the phase contact is established by a hydrophilic hollow-fiber membrane (polyacrylonitrile). The lipase is immobilized onto a spongy layer by pressurized adsorption. The productivity is about 40 kg trans-(2R,3S)-(4-methoxyphenyl) glycidic acid methyl ester m-2 a-1. This process has been operated since 1993. 

Kinetic Resolution of Glycidic Acid Methyl Ester by Lipase from Serratia marcescens (E.C. 3.1.1.3) 1430... 

A chiral intermediate (2R,iiS)-3-(4-methoxyphenyl)glycidic acid methyl ester [(—)-MPGM] 76 is required for the synthesis of diltiazem 72, a calcium channel antagonist. Matsumae et al. [Ill] screened over 700 microorganisms and identified lipase from Ser-... 

In the enz3miatic hydrolysis of racemic 3-(4-methox5rphenyl)glycidic acid methyl ester in SCCO2 the initial rate of the 2S,3R) isomer was faster than the rate of the 2R,3S) isomer [65]. An immobilized lipase from Mucor miehei was used. The stereoisomeric excess of the (2R,3S) form reached 87% at 53% total conversion level. No effects of water content of the reaction mixture and initial concentration of the racemate on isomeric purity was foxmd. The reaction rate was faster in SCCO2 than in toluene/water. 

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