RESUMO
Statins are inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase) and became the standard of care for treatment of hypercholesterolemia because of their efficacy, safety, and long-term benefits. They are administered as diastereo- and enantiomerically pure compounds. We summarize here two new approaches for the total synthesis of the most important representatives, atorvastatin, and rosuvastatin, based on highly stereoselective hydrogenations as key-steps.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/síntese química , Atorvastatina , Fluorbenzenos/síntese química , Fluorbenzenos/química , Ácidos Heptanoicos/síntese química , Ácidos Heptanoicos/química , Hidrogenação , Pirimidinas/síntese química , Pirimidinas/química , Pirróis/síntese química , Pirróis/química , Rosuvastatina Cálcica , Estereoisomerismo , Sulfonamidas/síntese química , Sulfonamidas/químicaRESUMO
Hydrogenation of chiral 2,2'-functionalized 1,1'-binaphthyls with Pd and Ru solid-supported metal catalysts was found to be a clean and convenient pathway to 5,5',6,6',7,7',8,8'-octahydro-1,1'-dinaphthyl derivatives. In most cases no racemization was observed in the course of the reaction.
RESUMO
Results achieved by the authors in the synthesis of chiral P,N-phosphite ligands are summarized. Three groups of new chiral P,N-phosphites are discussed, namely, ligands derived from 1,1'-bi-2-naphthol, ligands possessing an acyclic phosphorus center, and P*-chiral ligands derived from (S)-2-anilinomethylpyrrolidine. An overview of complexation of the ligands with Rh(I) and Pd(II) precursors is given. Accessibility and stability of chiral phosphite ligands possessing acyclic phosphorus was analyzed for the first time along with their efficiency in terms of stereoselectivity. The title ligands are shown to be highly efficient in the Pd-catalyzed allylic alkylation (up to 85% ee) and, especially, allylic sulfonylation (up to 97% ee) reactions in certain cases outperformed all known catalytic systems.