抄録
Kaitocephalin (1), isolated from Eupenicillium shearii PF1191 by Seto and Shin-ya et al., is known to exhibit a potent inhibitory activity against neuronal cell death by the antagonistic action on AMPA as well as NMDA glutamate receptors. This natural product has, therefore, considerable potential as a promising lead compound for developing therapeutic agents against neuronal diseases such as stroke and epilepsy. However, its detailed neurobiological study becomes very difficult at present because the fungus has not produced kitocephalin. Due to such extremely low availability from natural sources as well as the intriguing biological activity and synthetic challenges, kaitocephalin (1) has attracted much attention in the chemical and biological communities. Thus, there have been a number of synthetic studies including total syntheses achieved by five groups. In this symposium, we will report a new approach to 1, which relies on a C-H amination reaction of a sulfamate followed by formation of a pyrrolidine skeleton by nucleophilic opening of the resulting cyclic sulfamate. Thus, Rh(II)-catalyzed C-H amination reaction of 2lusing Rh_2(esp)_2 gave 22, which, upon tert-butoxycarbonylation and base treatment, produced pyrrolidine 24. 24 was converted to advanced key intermediate 30 via another Rh(II)-catalyzed C-H amination reaction for the introduction of a nitrogen atom at the allylic position of the cyclopenten ring of 26 giving 27 and installation of the 3-5-dichloro-4-acetoxybenzoyl group. From 30, the key precursor 31 for the synthesis of 1 was successfully synthesized by ozonolysis followed by Ru04-catalyzed oxidative cleavage.
