RESUMO
Mild substitution reactions of acetals with carbon nucleophiles via the pyridinium-type salts generated by the treatment of acetals with TESOTf-2,4,6-collidine or 2,2'-bipyridyl have been developed. Various carbon nucleophiles, such as organocuprates, silyl enol ethers, enamines, etc., reacted with the pyridinium-type salts to give the corresponding substituted products in good yields. The reactions proceeded under very mild conditions (non-acidic conditions) and thus acid-sensitive functional groups can be tolerated during the reaction. In addition, only an acetal can form the pyridinium-type salt and react with nucleophiles in the presence of a ketal. This unusual selectivity is in contrast to general methods conducted under acidic conditions.
Assuntos
Acetais/química , Carbono/química , Compostos de Piridínio/química , Ácidos/química , Estrutura Molecular , Piridinas/químicaRESUMO
The concise asymmetric total synthesis of scyphostatin has been achieved by condensation of the optically active cyclohexane unit, prepared from the commercially available 1,4-cyclohexadiene by our own method, and the side chain, prepared by the method developed by Hoye and Tennakoon (T. R. Hoye, M. A. Tennakoon, Org. Lett. 2000, 2, 1481-1483). The modification of the epoxy cyclohexenone unit was achieved in a late stage of the total synthesis, and deprotection of the primary alcohol was conducted in the final step. During the synthesis several key reactions were attained: 1) intramolecular bromoetherification of the cyclohexadiene acetal; 2) stereoselective introduction of the tertiary alcohol, 3) deprotection of the acetal function to the aldehyde by combination with silyl triflate/2,4,6-collidine and the one-pot synthesis of the disilyl aldehyde compounds, with different types of silyl groups, from the dihydroxy acetal compounds; and 4) facile deprotection of the 2,4-dimethoxyphenylmethyl ((2,4)DMPM) protecting group of the primary alcohol.
Assuntos
Amidas/síntese química , Amidas/farmacologia , Inibidores Enzimáticos/síntese química , Pironas/síntese química , Pironas/farmacologia , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Acetais/síntese química , Acetais/química , Álcoois/química , Aldeídos/química , Amidas/química , Cicloexenos/síntese química , Cicloexenos/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Hidroxilação , Estrutura Molecular , Nitrogênio/química , Pironas/química , Esfingomielina Fosfodiesterase/metabolismo , EstereoisomerismoRESUMO
A mild and efficient method for the preparation of O,O-mixed, O,S- and N,O-acetals from symmetrical O,O-acetals has been developed. Thus, the treatment of symmetrical O,O-acetals with TESOTf and 2,4,6-collidine formed weakly electrophilic collidinium salts. The addition of nucleophiles, such as an alcohol, lithium thioxide, and sodium azide, to the salts afforded the corresponding O,O-mixed, O,S- and N,O-acetals in good yields. The reaction proceeded under weakly basic conditions. No overreaction then occurred and many acid-labile functional groups could remain intact.