Arthrobacter sp.: a lipase of choice for the kinetic resolution of racemic arylazetidinone precursors of taxanoid side chains

The native strain of Arthrobacter sp. (MTCC 5125) bearing a lipase has been found to be the most effective in the kinetic resolution of racemic arylazetidinones for producing cis-(3R,4S)-3-acetoxy-1-(4-methoxyphenyl)-4-phenyl-2-azetidinone, cis-(3R,4S)-3-acetoxy-1-(4-methoxyphenyl)-4-(2-furanyl)-2-azetidinone, cis-(3R,4S)-3-acetoxy-1-(4-methoxyphenyl)-4-(2-thienyl)-2-azetidinone, and cis-3-acetoxy-4-(t-butyl)-2-azetidinone products. The resolved compounds, which were obtained in high enantiopurity are important intermediates of amino acid side chains of paclitaxel as well as a new generation of taxanoids. The use of co-solvents dramatically improved the resolution efficacy of the lipase.

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(+)-cis-(3R,4S)-3-Propyloxy-1-(4-methoxyphenyl)-4-phenyl-2-azetidinoneC19H19NO4Ee >99.5% (HPLC analysis)[α]D25=+3.5 (c 0.6, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (3R,4S)

(+)-cis-(3R,4S)-3-Butyloxy-1-(4-methoxyphenyl)-4-phenyl-2-azetidinoneC20H21NO4Ee >99.5% (HPLC analysis)[α]D25=+7.6 (c 0.54, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (3R,4S)

(+)-cis-(3R,4S)-3-Butyloxy-1-(4-methoxyphenyl)-4-phenyl-2-azetidinoneC22H25NO4Ee >99.5% (HPLC analysis)[α]D25=+11.6 (c 1, CHCl3)Source of chirality: enzymatic hydrolysisAbsolute configuration: (3R,4S)