RESUMO
O-Methylasparvenone (1) and asparvenone (2) were isolated from an Aspergillus parvulus Smith broth in a microbial screening for 5-HT2C ligands and found to be 5-HT2C antagonists. They represent the first nitrogen-free serotonin ligands. The absolute configuration of 1 was determined to be S by X-ray analysis of the corresponding Mosher-ester. A short and efficient synthesis of rac-1 was developed. This protocol was applied to the synthesis of derivatives of 1 and a structure-affinity relationship was established.
Assuntos
Naftóis/isolamento & purificação , Antagonistas da Serotonina/isolamento & purificação , Células 3T3 , Animais , Aspergillus , Camundongos , Modelos Moleculares , Naftóis/farmacologia , Ensaio Radioligante , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Relação Estrutura-AtividadeRESUMO
Resolution of (RS)-tetrindole (3) and enantioselective reductions of the imine 7 yielded (S)-(+)-(4) and (R)-(-)-tetrindole (5). The absolute stereochemistry of 4 was established by X-ray analysis of the corresponding Mosher amide 6. From in vitro as well as in vivo data (MAO-inhibition, levels of monoamines and their respective metabolites in rat brain), 4 was identified as the eutomer.
