Bös M, Canesso R, Inoue-Ohga N, Nakano A, Takehana Y, Sleight A J
Pharma Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Bioorg Med Chem. 1997 Dec;5(12):2165-71. doi: 10.1016/s0968-0896(97)00160-0.
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.
在针对5-HT2C配体的微生物筛选中，从小球曲霉史密斯肉汤中分离出了O-甲基天冬酰胺（1）和天冬酰胺（2），发现它们是5-HT2C拮抗剂。它们是首批无氮血清素配体。通过对相应莫舍尔酯的X射线分析确定1的绝对构型为S。开发了一种简短而有效的外消旋-1合成方法。该方法应用于1的衍生物合成，并建立了结构-亲和力关系。
