Yohimban-17-one

The chiroptical properties and conformations inferred therefrom were correlated " with n.m.r. and dehydrogenation (at C-3—N-4) measurements, the traditional methods for the analysis of configuration and conformation in these systems. The C-3 equilibration of all the yohimbane and yohimban-17-ones was studied. One interesting point which emerged was the differences observed between equilibrium positions determined by the usual organic acid method and... 

To a mixture of 886 g yohimbine (1) and 7.55 L dry dimethyl sulfoxide was added 5.05 L acetic anhydride. The mixture was stirred at room temperature for 18 h, then diluted with 16.8 L ethanol, stirred for 1 h, and mixed with 4.2 L water. Concentrated ammonium hydroxide (11 L) was added while maintaining the temperature at 15-30°C by cooling. The mixture was then diluted with 16.8 L water. Filtration gave a solid that was washed with water and dried to give 818 g (93%) of tan crystals, with a m.p. of 248-250°C (dec.). A slurry of this tan crystal was formed twice with 4 L ethanol, and 742 g methyl yohimban-17-one 16a -carboxylate (2) was obtained by filtration, in a yield of 84%, m.p. 253-254°C (dec.). 

Wolff-Kishner reduction of epifl//oyohimban-17-one affords a mixture of alio- and epm/Zoyohimbanes in contrast to the complete conversion of pieMt/oyohimban-17-one to yohimbane. 

One application of this reaction was in the synthesis of yohimban 11.17 (Scheme 11.6). The cycloaddition precursor 11.14 could be easily built up from tryptamine 11.13 and the cyclization employed a nickel/phosphite catalyst system. Selective reduction of the less-hindered alkene, protio-desilylation and a Bischler-Napieralski reaction gave the desired pentacyclic system 11.16. Reduction of the remaining alkene gave yohimban 11.17... 

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