RESUMO
Described herein is the synthesis of BMS-986001 by employing two novel organocatalytic transformations: 1)â a highly selective pyranose to furanose ring tautomerization to access an advanced intermediate, and 2)â an unprecedented small-molecule-mediated dynamic kinetic resolution to access a variety of enantiopure pyranones, one of which served as a versatile building block for the multigram, stereoselective, and chromatography-free synthesis of BMS-986001. The synthesis required five chemical transformations and resulted in a 44% overall yield.
Assuntos
Fármacos Anti-HIV/síntese química , Timidina/análogos & derivados , Fármacos Anti-HIV/química , Catálise , Levamisol/química , Estereoisomerismo , Timidina/síntese química , Timidina/químicaRESUMO
[reaction: see text] An efficient asymmetric synthesis of the vasopeptidase inhibitor BMS-189921 was accomplished. Two short enantioselective syntheses of the common key intermediate (S)-alpha-aminoazepinone 6b were developed. Olefin 3 was converted to 6b via asymmetric hydrogenation. Alternatively, enyne 12 was converted to racemic alpha-aminoazepinone 15b, which was transformed to 6b by a practical dynamic resolution.
Assuntos
Azepinas/química , Azepinas/síntese química , Endotélio Vascular/enzimologia , Inibidores Enzimáticos/síntese química , Neprilisina/antagonistas & inibidores , Azepinas/farmacologia , Inibidores Enzimáticos/farmacologia , Hidrogenação , EstereoisomerismoRESUMO
A highly stereoselective synthesis of the novel tryptase inhibitor BMS-262084 was developed. Key to this synthesis was the discovery and development of a highly diastereoselective demethoxycarbonylation of diester 12 to form the trans-azetidinone 13. BMS-262084 was prepared in 10 steps from D-ornithine in 30% overall yield.