A novel strategy towards the atorvastatin lactone
2010; Elsevier BV; Volume: 66; Issue: 51 Linguagem: Inglês
10.1016/j.tet.2010.10.028
ISSN1464-5416
AutoresPramod Sawant, Martin E. Maier,
Tópico(s)HIV/AIDS drug development and treatment
ResumoWe describe a novel strategy to the atorvastatin lactone based on a Paal–Knorr synthesis of pyrrole 24 by condensing diketone 23 with primary amine 22. The latter contains the syn-1,3-diol subunit and a benzyl ether function at the other end of the chain. This allowed for manipulations on the pyrrole ring via iodination at C2, metalation with t-BuLi and carboxylation. The obtained acid 26 could be converted via amide formation, debenzylation, oxidation and lactonization to atorvastatin lactone 6. The key building block, 2-((4R,6S)-6-(2-(benzyloxy)ethyl)-2,2-dimethyl-1,3-dioxan-4-yl)ethanamine (22) was obtained by two sequential asymmetric transfer hydrogenative carbonyl allylations according to Krische.
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