Synthesis of aspidospermidine alkaloids from 1,2,3,4-tetrahydrocarbazole: Total stereoselective synthesis of (±)-18-noraspidospermidine

Abstract

The reactivity of the 1,2,3,4-tetrahydrocarbazol-4-one derivatives has been analysed and applied to the synthesis of (±)-18-noraspidospermidine ( 1b). This was synthesised, starting from 4-(1′,3′-dioxolan-2′-yl)cyclohexanone which was successively transformed to 3-methyl-3-(3′-nitropropyl)-1,2,3,4-tetrahydrocarbazol-4-one and to the imine tetracycle 13 by means of nickel boride catalyst. The reduction of 13 to the natural cis D ring junction was carried out with the LiAlH 4 AlCl 3 system. The construction of the E-ring was carried out by a Pummerer type reaction from the cis-7-tosyl-1-phenylthioacetamide derivative 17 by oxidation followed by intramolecular cyclisation, desulfurization and reduction to 1b.