A stereorational total synthesis of (−)-ptilocaulin

A stereorational total synthesis of the structurally (?)-enantiomer of the unique guanidine containing natural product ptilocaulin is described. This efficient synthesis (14 steps, 7.4% overall yield) utilizes an intramolecular 1,3-dipolar cycloaddition as a key step and establishes that the natural product is the most stable of a number of possible isomers. This work also establishes the absolute stereochemistry of ptilocaulin to be that shown in formula 3.