O-METHYLASPARVENONE, A NITROGEN-FREE SEROTONIN ANTAGONIST

O-Methylasparvenone (1) and asparvenone (2) were isolated from an Aspe rgillus parvulus Smith broth in a microbial screening for 5-HT2C ligan ds and found to be 5-HT2C antagonists. They represent the first nitrog en-free serotonin ligands. The absolute configuration of 1 was determi ned to be S by X-ray analysis of the corresponding Mosher-ester. A sho rt and efficient synthesis of rac-1 was developed. This protocol was a pplied to the synthesis of derivatives of 1 and a structure-affinity r elationship was established. (C) 1997 Elsevier Science Ltd.