Novel chemo-enzymatic route to a key intermediate for the taxol side-chain through enantioselective O-acylation. Unexpected acyl migration

• Enzymatic acylation (E > 200) of primary OH with remote stereocentre was achieved.
• Intramolecular acyl migration was detected between OCOMe and OH functions.
• (2R,3S)-3-Phenylisoserine hydrochloride (ee = 99%), a key intermediate for the taxol side-chain was prepared.

A new enzymatic strategy has been devised for the preparation of a key intermediate for the taxol side-chain from N-hydroxymethylated cis-3-acetoxy-4-phenylazetidin-2-one. Burkholderia cepacia (PS-IM)-catalyzed acylation of the primary OH group with an excess of vinyl butyrate (10 equiv.) furnished the corresponding diester and unreacted monoester with excellent enantiomeric excess values (ee ≥ 98%). Traces of undesirable enantiomeric diacetylated product and diol due to intramolecular acyl migration (∼6% mole fractions) were also detected. Finally, (2R,3S)-3-phenylisoserine hydrochloride (ee = 99%), a key intermediate for the taxol side-chain, was prepared from the corresponding diester enantiomer through acidic hydrolysis.

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