RESUMEN
An efficient, stereoselective synthesis of 4'-Ed4T is demonstrated. The synthesis is highlighted by a regioselective TMSOTf-mediated acetal opening, a Claisen rearrangement to set the key 4'-stereocenter as well as the olefin, and a one-pot nonaflation/elimination to deliver the alkyne moiety. The synthesis proceeds in eight steps from 5-methyluridine and occurs in 37% overall yield.
Asunto(s)
Estavudina/análogos & derivados , Uridina/análogos & derivados , Alquenos/química , Alquinos/química , Estructura Molecular , Estavudina/síntesis química , Estavudina/química , Estereoisomerismo , Uridina/síntesis química , Uridina/químicaRESUMEN
Stereoselective reduction of dehydroalanine double bond in nocathiacin I afforded the primary amide 2. Enzymatic hydrolysis of the amide 2 provided the carboxylic acid 3, which upon coupling with a variety of amines furnished amides 4-32. Some of these semi-synthetic derivatives have retained very good antibacterial activity and have improved aqueous solubility.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Enterococcus faecalis/efectos de los fármacos , Péptidos/síntesis química , Péptidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Antibacterianos/química , Técnicas In Vitro , Péptidos y Proteínas de Señalización Intercelular , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Péptidos/química , Solubilidad , Estereoisomerismo , Relación Estructura-Actividad , Agua/químicaRESUMEN
We have evaluated various achiral templates (1a-g, 10, and 16) in conjunction with chiral Lewis acids in the conjugate addition of nucleophilic radicals to alpha-methacrylates followed by enantioselective H-atom transfer. Of these, a novel naphthosultam template (10) gave high enantioselectivity in the H-atom-transfer reactions with ee's up to 90%. A chiral Lewis acid derived from MgBr(2) and bisoxazoline (2) gave the highest selectivity in the enantioselective hydrogen-atom-transfer reactions. Non-C(2) symmetric oxazolines (20-25) have also been examined as ligands, and of these, compound 25 gave optimal results (87% yield and 80% ee). Insights into rotamer control in alpha-substituted acrylates and the critical role of the tetrahedral sulfone moiety in realizing high selectivity are discussed.
