RESUMO
A detailed examination of [4+2] cycloaddition reactions between 1,8-disubstituted cyclooctatetraenes and diazo compounds revealed that 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) reacts to form either 2,3- or 3,4-disubstituted adducts. The product distribution can be controlled by modulating the electron density of the cyclooctatetraene. Unprecedented [4+2] cycloadditions between diisopropyl azodicarboxylate (DIAD) and 1,8-disubstituted cyclooctatetraenes are also described and further manipulation of a resulting cycloadduct uncovered a new pathway to the synthetically challenging bicyclo[4.2.0]octa-2,4-diene family. Variation of the substituents resulted in a range of compounds displaying selective action against different human tumour cell types.
Assuntos
Antineoplásicos/síntese química , Compostos Azo/química , Compostos Bicíclicos com Pontes/síntese química , Diterpenos/síntese química , Micro-Ondas , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Ciclização , Humanos , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo , Triazóis/químicaRESUMO
The gas phase anion proton affinities of the periodinane anions IBX- and IBA- were examined using mass spectrometry-based experiments, and estimated as 1300 +/- 25 and 1390 +/- 10 kJ mol(-1), respectively. The experimental results were supported by theoretical calculations, which yielded proton affinities of 1336 and 1392 kJ mol(-1) for IBX- and IBA- respectively, at the B3LYP/aug-cc-PVDZ level of theory.
Assuntos
Gases/química , Iodobenzoatos/química , Prótons , Ânions/química , Iodobenzenos , Cinética , Espectrometria de MassasRESUMO
The total synthesis of (+/-)-5,14-bis-epi-spirovibsanin A was achieved in 18 steps. Physical data obtained from (+/-)-5,14-bis-epi-spirovibsanin A lends strong support to the proposed connectivity and relative stereochemistry of spirovibsanin A.
Assuntos
Diterpenos/síntese química , Compostos de Espiro/síntese química , Ciclização , Diterpenos/química , Estrutura Molecular , Plantas Medicinais/química , Compostos de Espiro/química , Estereoisomerismo , Viburnum/químicaRESUMO
Synthesis and preliminary in vitro biological evaluation of a selective high-affinity CRTH2 antagonist is described. The stability of an N-benzyl group facilitated synthesis of the corresponding radioligand by tritiation of a brominated precursor. The compound [(3)H]TRQ11238 represents the first selective CRTH2 antagonist radioligand and exhibited a specific radioactivity of 52 Ci/mmol and a pK(d) of 9.0.
