Synthesis of (-)-7-epiaustraline and (-)-1-epicastanospermine

Highly efficient and selective syntheses of the title compounds are describ ed. The cornerstone of the synthetic plan is the tandem inter [4 + 2]/inter [3 + 2] cycloaddition process. These syntheses differ from previous applic ations of this strategy in that they incorporate an alkylation in the hydro genolysis step to close the second ring of the azabicyclic systems. Notable features of the sequence are (1) the highly regio- and stereoselective [3 + 2] cycloaddition of nitronate 15 with siloxymethyl (Z)-beta-silylvinyl ke tone (Z)-22b and (2) the highly selective reduction of the resulting ketone 24a with L-Selectride. A single-crystal X-ray structure analysis of synthe tic (-)-7-epiaustraline confirmed that the targeted structure was successfu lly synthesized. This stimulated a reexamination of the structural assignme nt of the natural product. (-)-1-Epicastanospermine was synthesized in four steps from the common intermediate 27a. The absolute configuration of (-)- 1-epicastanospermine was assured by single-crystal X-ray structure analysis of intermediate (-)-27a. Thus, the sign of the optical rotation had to be revised. The overall efficiency of these syntheses were 9 steps and 23% yie ld for (-)-7-epiaustraline and 10 steps and 20% yield for (-)-1-epicastanos permine.