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

The N‐Hydroxymethyl Group as a Traceless Activating Group for the CAL‐B‐Catalysed Ring Cleavage of β‐Lactams: A Type of Two‐Step Cascade Reaction

“…A recent observation that the lactam ring of N ‐hydroxymethyl‐ cis ‐3‐acetoxy‐4‐phenylazetidin‐2‐one was partially opened during CAL‐B (30 mg mL –1 )‐catalysed O ‐acetylation (0.015 M substrate, 6 equiv. of vinyl‐acetate, i Pr 2 O, 50 °C),14 combined with results on the CAL‐B‐catalysed ring cleavage of inactivated β‐lactams,7a,7e suggested the possibility of CAL‐B‐catalysed ring‐opening of (3 S *,4 R *)‐(±)‐ 1 . It is noteworthy that only one of the earlier works dealing with the acylation of N ‐hydroxymethyl‐β‐lactams8d,15 noted the use of CAL‐B (30 mg mL –1 ) as an optimum catalyst for the acylation of 9‐azabicyclo[6.2.0]dec‐4‐en‐10‐one (1 equiv.…”

Recent Advances in Lipase-Mediated Preparation of Pharmaceuticals and Their Intermediates

“…The reaction was conducted with a higher amount of substrate (100 mg) and, after 20 min, the conversion reached 50%, with the formation of the diester (3 R ,4 S ) with >99% ee and the remaining substrate (3 S ,4 R ) with 98% ee , and E > 200, with traces of a byproduct from the migration of the acyl group. Both the (3 R ,4 S )-diester and the remaining (3 S ,4 R )-substrate were subjected to acid hydrolysis leading to (2 R ,3 S )-3-phenylisoserine hydrochloride with >99% ee (key intermediate for the Paclitaxel side chain) and (2 S ,3 R )-3-phenylisoserine hydrochloride with 98% ee [ 58 ].…”

“… Enzymatic kinetic resolution of racemic N -hydroxymethylated cis -3-acetoxy-4-phenylazetidin-2-one ( rac -azetidin-2-one derivative), affording the key intermediate for the Paclitaxel side chain, (2 R ,3 S )-3-phenylisoserine [ 58 ]. …”