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

The reactivity of the 1,2,3,4-tecrahydrocarbazol-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 LiAlH4/AlCl3 system. The construction of the E-ring was carried out by a Pummerer type reaction from thecis-7-tosyl-1-phenylthioacetamide derivative 17 by oxidation followed by intramolecular cyclisation, desulfurization and reduction to 1b. (C) 1999 Elsevier Science Ltd. All rights reserved.