RESUMO
A simple protocol for the synthesis of Weinreb benzamides and alpha,beta-unsaturated Weinreb amides through a palladium-catalyzed cross-coupling reaction between organoboronic acids and N-methoxy-N-methylcarbamoyl chloride has been developed. The method is also applicable to the use of potassium organotrifluoroborates.
Assuntos
Amidas/química , Ácidos Borônicos/química , Carbamatos/química , Alcenos/química , Catálise , Ciclização , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Paládio , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
The desmethoxy analogue of the cytotoxic, cyclic depsipeptide callipeltin B was synthesized to evaluate the role of its beta-MeOTyr residue. The IC(50) of desmethoxycallipeltin B, in which the beta-MeOTyr residue was replaced by d-Tyr, against HeLa cells was found to be 128+/-10 microM in an MTT assay, compared to 98+/-5 microM for the natural product itself. The roughly comparable cytotoxicities suggest that the cytotoxicity of callipeltin B does not arise through the formation of a quinone methide intermediate.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Indolquinonas/química , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Antineoplásicos/química , Espectroscopia de Ressonância Magnética , Peptídeos Cíclicos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
The cytotoxic, cyclic heptadepsipeptide, natural product callipeltin B was synthesized on a solid-phase support in 15% overall yield. Comparison of the 1H NMR spectra of three synthetic isomers with those of callipeltin B confirmed the configurational reassignment of its threonine residues as d-allothreonine and the assignment of the configuration of its beta-methoxytyrosine residue as (2R,3R).
Assuntos
Depsipeptídeos/síntese química , Peptídeos Cíclicos/síntese química , Animais , Depsipeptídeos/química , Depsipeptídeos/isolamento & purificação , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Poríferos/química , Conformação ProteicaRESUMO
The absolute stereochemistry of the three unresolved structural components in neamphamide A (1) was determined to be (R)-beta-methoxy-L-tyrosine, (2R,3R,4S)-4-amino-7-guanidino-2,3-dihydroxyheptanoic acid, and (2R,3R,4R)-3-hydroxy-2,4,6-trimethylheptanoic acid. Stereochemical assignments were made by chemical degradation of 1, derivatization of the resulting products, and then spectroscopic and chromatographic comparison of the derivatives with synthetically prepared standards. Using the same analytical protocol developed for 1, the beta-methoxytyrosine residue in papuamide B (2) was found to be (R)-beta-methoxy-D-tyrosine. This represents a rare example of divergent stereochemistry in an unusual amino acid residue that is present in two closely related classes of peptides.
