This project is a continuation of the current project of the same title which has now been pursued for two and a half years. The goal is the total stereocontrolled synthesis of the alkaloid germine. That substance is of considerable interest for two reasons: Biologically, germine ester happen to be the most active of the hypotensive Veratrum alkaloids. These substances, which have a medicinal history going back several hundred years, have a degree of complexity which has kept them beyond the reach of synthesis. Secondly, the degree of complexity implicit in the hexacyclic system with its sixteen asymmetric centers strongly implies that a solution to the synthetic challenge would be a considerable contribution to extending the methodology available for the construction of complex three-dimensional arrays. It might be pointed out, in passing, that this number of asymmetric centers is considerable, even by today's standards: Most of the constructions which appear to reach such numbers are really the joining together of fragments of relatively small numbers of chiral centers. The claim is then often made that a substance with, say, eighteen asymmetric centers has been assembled, when it would be more accurate to say that three six-center problems have been solved, and the resulting pieces have then been joined. Otherwise, the linking of fifty optically active aminoacids would have to be considered a total synthesis of a substance with fifty asymmetric centers, achieved with complete stereochemical control. Such a view might be legally compelling, but would be chemically misleading.
