Tandem cleavage of hydrogenated β- and γ-carbolines - New practical synthesis of tetrahydroazocino[4,5-b]indoles and tetrahydroazocino[5, 4-b]indoles showing acetylcholinesterase inhibitory activity

Hydrogenated γ-carbolines underwent tandem piperidine ring cleavage on treatment with dimethyl acetylenedicarboxylate (DMAD) or ethyl propiolate (EP) in the presence of alcohols, producing 3-alkoxymethyl-substituted indoles in high yields. These compounds were cyclized to tetrahydroazocino[4,5-b]indoles in the presence of AlCl3. Hydrogenated β-carbolines produced tetrahydroazocino [5,4-b]indoles directly upon treatment with EP in ethanol. The resulting azocinoindole derivatives were subjected to a preliminary evaluation of their in vitro acetylcholinesterase (AChE) inhibitory activities. Most of them were found to inhibit AChE with IC50 values in the micromolar range, compound 17 being the most potent (IC50 = 8.7 μm). © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004