Facile and Highly Enantioselective Synthesis of (þ)- and (-)-Fluvastatin and Their Analogues
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Statins represent a class of drugs that are capable of
regulating the biosynthesis of cholesterol by inhibiting the
enzyme that reduces 3-hydroxy-3-methylglutaric acid to
mevalonic acid, namely, the HMG-CoA reductase inhibitors.
Since the introduction of pravastatin by Sankyo and
lovastatin by Merck to the pharmaceutical market, this class
of drugs has been in eminent demand. Due to the importance
of these drugs, various synthetic strategies aimed at the construction
of statins have been reported.Many of these studies
have focused on the introduction of the statin side chain.1
During the course of our efforts to develop a facile synthesis
of HMG-CoA reductase inhibitors, a three-step linear synthesis
of fluvastatin 5 has been identified and successfully
implemented. Most of the statins, such as atorvastatin calcium
hydrate, simvastatin, and pravastatin sodium, are administered
in the optically pure form. However, to our knowledge,
fluvastatin has been approved as a racemic form. Actually,
Novartis’ group reported manufacturing process for fluvastatin
in racemic form.2 As for chiral version, Prasad and his