Biocatalyzed Synthesis of Statins: A Sustainable Strategy for the Preparation of Valuable Drugs

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ID: 51283
2019
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Abstract
Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the largest selling class of drugs prescribed for the pharmacological treatment of hypercholesterolemia and dyslipidaemia. Statins also possess other therapeutic effects, called pleiotropic, because the blockade of the conversion of HMG-CoA to (R)-mevalonate produces a concomitant inhibition of the biosynthesis of numerous isoprenoid metabolites (e.g., geranylgeranyl pyrophosphate (GGPP) or farnesyl pyrophosphate (FPP)). Thus, the prenylation of several cell signalling proteins (small GTPase family members: Ras, Rac, and Rho) is hampered, so that these molecular switches, controlling multiple pathways and cell functions (maintenance of cell shape, motility, factor secretion, differentiation, and proliferation) are regulated, leading to beneficial effects in cardiovascular health, regulation of the immune system, anti-inflammatory and immunosuppressive properties, prevention and treatment of sepsis, treatment of autoimmune diseases, osteoporosis, kidney and neurological disorders, or even in cancer therapy. Thus, there is a growing interest in developing more sustainable protocols for preparation of statins, and the introduction of biocatalyzed steps into the synthetic pathways is highly advantageous—synthetic routes are conducted under mild reaction conditions, at ambient temperature, and can use water as a reaction medium in many cases. Furthermore, their high selectivity avoids the need for functional group activation and protection/deprotection steps usually required in traditional organic synthesis. Therefore, biocatalysis provides shorter processes, produces less waste, and reduces manufacturing costs and environmental impact. In this review, we will comment on the pleiotropic effects of statins and will illustrate some biotransformations nowadays implemented for statin synthesis.
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hoyos2019biocatalyzedcatalysts Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Hoyos, Pilar;Pace, Vittorio;Alcántara, Andrés R.;
Journal catalysts
Year 2019
DOI
DOI not found
URL
http://www.mdpi.com/2073-4344/9/3/260
Keywords
chemistry Veterinary medicine Medicine (General) Chemical technology public aspects of medicine social sciences (general) social sciences social pathology. social and public welfare. criminology animal culture diseases of the genitourinary system. urology law in general. comparative and uniform law. jurisprudence

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