6 Alangimarckineの合成と絶対構造

抄録

With a view to establishing the absolute stereochemistry of the Alangium alkaloid alangimarckine, the target stereoformula III was selected for synthesis. Condensation of tricyclic amino acid (-)-IX, prepared from cincholoipon ethyl ester [(+)-VI] according to previously reported procedure, with tryptamine by the diethyl phosphorocyanidate method gave tryptamide (+)-X (92% yield), which was then cyclized (POCl_3, boiling toluene) to (+)-XI in a good yield. Catalytic hydrogenation of (+)-XI (Pt/H_2, dioxane) and chromatographic separation of products afforded base (+)-XII (25% yield) and its 1'-epimer [(-)-XIII](48% yield). The two bases were separately debenzylated (Pd-C/H_2, MeOH-AcOH) to produce the corresponding phenolic bases, (-)-III and (-)-XIV, in good yields. The absolute configuration at C-1' of (-)-III and (-)-XIV was confirmed by comparison of their IR and NMR spectra and thin-layer chromatographic mobility with those of the corresponding racemic modifications of established stereochemistry. It was also supported by comparison of their CD spectra in ethanol or 0.1 N hydrochloric acid with those of emetine (XV)-isoemetine (XVI), ochrolifuanine A-ochrolifuanine B, and certain structural analogs of tubulosine. Since the synthetic base [(-)-III] has been found to match natural alangimarckine, the above results prove that stereoformula III is a complete expression for alangimarckine.