Total synthesis of the alkaloids rhoeadine and alpinigenine

Abstract

Rhoeadine (I) and alpinigenine (III) have been synthesised by a route involving the skeletal rearrangement of 1,2,3,4-tetrahydro-2-methyl-4′,5′,6,7-bismethylenedioxyisoquinoline-1-spiro-2′-indan-1′-ol (VII) into 5,6,7,7a-tetrahydro-2,3:10,11-bismethylenedioxy-7-methylbenz[d]indeno[1,2-b]azepine (VIII) by treatment with methanesulphonyl chloride and triethylamine. Oxidation of the indenoazepine (VIII) with osmium tetroxide gave 5,6,7,7a,12,12a-hexahydro-2,3:10,11-bismethylenedioxy-7-methylbenz[d]indeno[1,2-b]azepine-12,12a-diol (X), which was converted into (±)-rhoeagenine diol (XII) by treatment with sodium periodate followed by sodium borohydride. From 1,2,3,4-tetrahydro-2-methyl-4′,5′,6,7-tetramethoxy-1-spiro-2′-indan-1′-ol (XVII), (±)-alpinigenine diol (XXI) was synthesised. Oxidation of the diol (XXI) with manganese dioxide furnished (±)-alpinigenine (III).