RESUMO
A highly practical and modular synthesis to obtain a diverse 14-membered ring-based macrocyclic toolbox is achieved. These compounds were further tested in zebrafish assays related to early embryonic development, angiogenesis, and neurogenesis, respectively. 1.4c was identified as an antiangiogenesis agent.
Assuntos
Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/farmacologia , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/farmacologia , Inibidores da Angiogênese/química , Animais , Desenho de Fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Compostos Macrocíclicos/química , Estrutura Molecular , Morfogênese/efeitos dos fármacos , Neovascularização Patológica , Gravidez , Relação Estrutura-Atividade , Peixe-Zebra/embriologiaRESUMO
Schulzeines B (2) and C (3) were synthesized by a convergent strategy using epimeric tricyclic lactam building blocks, 4 and 5, and the C28 fatty acid side chain 6. Syntheses of tricyclic lactams (4/5) were achieved by Bischler-Napieralski reaction. Sharpless asymmetric dihydroxylation and BINAL-H-mediated asymmetric reduction of an enone was employed to prepare the key fatty acid side chain 6. The spectral as well as analytical data of 2 and 3 were in good agreement with the reported data for the natural products, thus confirming their assigned structures.