Enantioselective hydrolysis of 3,4-disubstituted β-lactams. An efficient enzymatic method for the preparation of a key Taxol side-chain intermediate

•CAL-B-catalysed ring-cleavage of 3,4-disubstituted β-lactams (E > 200).•A suitable method for the preparation of Taxol® side-chain was developed.•Debenzylation was performed in a continuous flow system by using 10% Pd/C.

3,4-Disubstituted β-lactams 3-benzyloxy-4-(4-chlorophenyl)azetidin-2-one [(3S*,4R*)-(±)-1], 3-benzyloxy-4-phenylazetidin-2-one [(3S*,4R*)-(±)-2] and 4-(4-chlorophenyl)-3-phenoxyazetidin-2-one [(3S*,4R*)-(±)-3] were resolved through immobilized CAL-B-catalysed ring-cleavage reactions. Excellent enantioselectivities (E > 200) were obtained for (3S*,4R*)-(±)-1 and (3S*,4R*)-(±)-2 when the reactions were performed with added H2O as nucleophile in tert-butyl methyl ether at 70 °C, whereas only moderate E (12) was achieved for (3S*,4R*)-(±)-3 under the same conditions but in diisopropyl ether. The resulting ring-opened β-amino acids [(2R,3S)-4 (ee > 98%), (2R,3S)-5 (ee > 98%) and (2R,3S)-6 (ee = 50%)] and the unreacted β-lactams [(3S,4R)-1–3] (ee > 98%) could be easily separated.

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