RESUMO
A formal total synthesis of the oxopentaene macrolide antibiotic RK-397 has been achieved. Nine stereocenters were established by a combination of allylation and our asymmetric hydration reactions and a 1,5 anti-selective aldol reaction. The synthesis proceeded in 19 steps from simple achiral conjugated dienoates.
Assuntos
Antibacterianos/síntese química , Macrolídeos/síntese química , Antibacterianos/química , Macrolídeos/química , Estrutura Molecular , EstereoisomerismoRESUMO
A de novo approach to the formal total synthesis of the macrolide natural product (-)-virginiamycin M2 has been achieved via a convergent approach. The absolute and relative stereochemistry of the nonpeptide portion of (-)-virginiamycin M2 was introduced by two Sharpless asymmetric dihydroxylation reactions.
Assuntos
Macrolídeos/síntese química , Virginiamicina/análogos & derivados , Virginiamicina/síntese química , Catálise , Macrolídeos/química , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo , Virginiamicina/químicaRESUMO
The enantioselective syntheses of several protected 4-substituted syn-3,5-dihydroxy carboxylic esters have been achieved from the corresponding achiral (E,E)- or (E,Z)-1,3-dienoates. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to form gamma-substituted delta-hydroxy-1-enoates. The resulting delta-hydroxy-1-enoates are subsequently converted into benzylidene-protected 4-substituted syn-3,5-dihydroxy carboxylic esters in one step. The benzylidene-protected 3,5-dihydroxy carboxylic esters are produced in good overall yields (20-54%) and high enantiomeric excess (73-97% ee).