573690-18-3Relevant academic research and scientific papers
A new and efficient synthesis of the HMG-CoA reductase inhibitor pitavastatin
Acemoglu, Murat,Brodbeck, Andre,Garcia, Angel,Grimier, Dominique,Hassel, Marc,Riss, Bernhard,Schreiber, Robert
, p. 1069 - 1081 (2007)
A new synthetic method for the preparation of pravastatin is described. The approach circumvents various synthetic problems associated with the buildup of the 3,5-dihydroxy-C7 acid side chain of HMG-CoA reductase inhibitors (statins). The use of the C6-amide derivative 5 instead of ester derivatives in the coupling reaction with carboxaldehyde 8 (Scheme 3) prevents undesired side reactions, such as eliminations and retro-aldol reactions. The method provides synthetic statins, such as pitavastatin, in >99% ee and exceptionally high overall yield. The enantiomerically pure starting material, (3S)-3-{[(tert-butyl)dimethylsilyl]oxy}-5-oxo-5-{[(1S)-1-phenylethyl]amino} pentanoic acid (3c), is prepared by an improved procedure from 3-{[(tert-butyl)dimethylsilyl]oxy}glutaric anhydride (1) and (1S)-1-phenylethylamine (2c; Scheme 1).
