Studies on the alkaloids of menispermaceous plants. CCXLIX. Total synthesis of optically active natural isotetrandrine, phaeanthine, and tetrandrine.

Abstract

Natural phaeanthine (1a), isotetrandrine (lb), and tetrandrine (1c), belonging to the oxyacanthine–berbamine series of the bisbenzylisoquinoline alkaloids, have been synthesised by a stepwise route. One of the benzyliso-quinoline nuclei was constructed initially, and joined by the Ullmann method through ether linkages to protected phenethylamine and phenylacetic acid units. The phenylacetic acid portion was activated by formation of its nitrophenyl ester and condensed with the phenethylamine unit (protected by a t-butoxycarbonyl group) to form a macrocyclic amide. The latter was converted by Bischler-Napieralski cyclisation and reduction into the desired alkaloids without formation of any structural isomers.