Atorvastatin Lipitor Enzymatic Desymmetrization of 3-Hydroxyglutaronitrile

In enzymatic diastereoselective hydrolysis process, a reactor was charged with water (4861) and sodium bicarbonate (17.3 kg), and the mixture was stirred until a solution was formed. Lipase PS-SD (10.8kg, 23000U/g) was charged, and the mixture was stirred until a solution was formed. The solution was transferred to a vessel containing substrate 45 in toluene, and the reaction was carried out at 45 °C for 48 h. From the reaction mixture, product 46 was isolated as a TBME solution (202.4 kg) containing 24.8kg of product with a 45.6% yield [79]. 

Atorvastatin (Lipitor) enzymatic desymmetrization of 3-hydroxy-glutaronitrile. 

17 ANTICANCER DRUGS ENZYMATIC SYNTHESIS OFTAXANE SIDE CHAIN 

BMS lipase and lipase PS-30 were immobilized on Accurel polypropylene (PP), and the immobilized lipases were used in tire hydrolytic reaction. Immobilized enzymes were reused over 10 cycles without tire loss of enz3une activity, productivity, or the ee of product 57. This process was scaled up to 2501 (2.5 kg substrate input) using immobilized lipase PS-30. From the reaction batch, R-acetate 57 was isolated with a 45 M% yield (theoretical maximum yield 50%) and 99.5% ee. The (R)-acetate was chemically converted to (R)-alcohol 54. The C-13 Paclitaxel side-chain synthon (R)-54 produced by the resolution process was coupled to baccatin 111 58 after protechon and deprotection to prepare Paclitaxel by a semisynthetic process [87,89]. 

Anticancer drugs enzymatic synthesis of taxane side chain. 

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