Preparative scale coupling cycle

In an alternate process for the preparation of the C-13 paclitaxel side chain, the enantioselective enzymatic hydrolysis of racemic acetate ci5 -3-(acetyloxy)-4-phenyl-2-azetidinone 38 (Eignre 16.10B), to the corresponding (S)-alcohol 39 and the nnreacted desired (l )-acetate 38 was demonstrated [63] nsing lipase PS-30 from Pseudomonas cepacia (Amano International Enzyme Company) and BMS lipase (extracellnlar lipase derived from the fermentation of Pseudomonas sp. SC 13856). Reaction yields of more than 48% (theoretical maximnm yield 50%) with EEs greater than 99.5% were obtained for the (R)-38. BMS lipase and lipase PS-30 were immobilized on Accnrel polypropylene (PP), and the immobilized lipases were reused (10 cycles) without loss of enzyme activity, productivity, or the EE of the product (R)-38. The enzymatic process was scaled up to 250 L (2.5 kg substrate input) using immobilized BMS lipase and lipase PS-30. Prom each reaction batch, R-acetate 38 was isolated in 45 mol% yield (theoretical maximum yield 50%) and 99.5% EE. The (R)-acetate was chemically converted to (R)-alcohol 39. The C-13 paclitaxel side-chain synthon (2R,3S-37 or R-39) produced by either the reductive or resolution process could be coupled to bacattin III 34 after protection and deprotection to prepare paclitaxel by a semisynthetic process [64]. 

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