RESUMEN
A novel acid-promoted rearrangement is disclosed. In the previously unknown transformation, an allyl group migrated to an in situ formed carbocation stabilized by an electron-rich aryl or heteroaryl group, resulting in a stereoselective intramolecular Grob fragmentation. The outcome of the rearrangement observed with an array of substrates can be satisfactorily rationalized using a working hypothesis with the aid of a six-membered transition state similar to those proposed for the anionic oxy-Cope or oxonia-Cope rearrangements, but involving only one instead of two double bonds.
Asunto(s)
Calcimicina/análogos & derivados , Acetatos/química , Calcimicina/síntesis química , Calcimicina/química , Difosfonatos/química , Peróxido de Hidrógeno/química , Policétidos/química , EstereoisomerismoRESUMEN
The synthesis of (-)-demethyl (C-11) cezomycin was achieved through an efficient route that features the use of a Kulinkovich reaction to couple two multifunctionality-containing fragments and a cascade of ring opening of cyclopropanol/1,5-hydrogen shift/desilylation-oxidation. The hidden yet undeniable problem of irreproducible specific rotation for this family of compounds was solved by sufficient acidification. The absolute configuration for the natural product was thus established as the mirror image of the synthetic sample.
Asunto(s)
Antibacterianos/síntesis química , Calcimicina/análogos & derivados , Antibacterianos/química , Calcimicina/síntesis química , Calcimicina/química , Hidrógeno/química , Oxidación-Reducción , EstereoisomerismoAsunto(s)
Ácidos Carboxílicos/química , Neurotransmisores/química , Fotoquímica , Animales , Calcimicina/análogos & derivados , Calcimicina/síntesis química , Calcimicina/química , Ácidos Carboxílicos/síntesis química , Línea Celular , Ácido Glutámico/análogos & derivados , Ácido Glutámico/síntesis química , Ácido Glutámico/química , Indicadores y Reactivos , Ionóforos/síntesis química , Ionóforos/química , Cinética , Neurotransmisores/síntesis química , Neurotransmisores/farmacología , Fotólisis , Receptores de Neurotransmisores/efectos de los fármacos , beta-Alanina/análogos & derivados , beta-Alanina/síntesis química , beta-Alanina/químicaRESUMEN
Ten semi-synthetic analogs of A23187 (calcimycin), with only the benzoxazole ring substituents modified together with the ionophore X14885A were studied with regard to their calcium and magnesium carrier properties through an organic phase (toluene - butanol, 70:30). The results indicate that the carboxylic group and the oxazolic nitrogen, maintained in the ortho position are essential for the ionophorous properties. Further, the introduction of a substituent in place of the NHCH3 group, producing steric hindrance of the carboxylic group leads to a destabilization of the 2:1 associations with cations.
Asunto(s)
Calcimicina/análogos & derivados , Benzoxazoles , Calcimicina/síntesis química , Calcimicina/farmacología , Calcio/metabolismo , Concentración de Iones de Hidrógeno , Magnesio/metabolismo , Relación Estructura-ActividadRESUMEN
Semisynthesis of two demethylamino A23187 with a methyl group in the 4- or 5-position on the benzene ring were carried out via the cleavage of A23187 oxazole ring and rebuilding of modified benzoxazoles. These compounds were shown to release Ca++ and MG++ from mitochondria and to keep part the antibacterial activity of the natural metabolite.