The first total synthesis and reassignment of the relative stereochemistry of 16-hydroxy-16,22-dihydroapparicine

We report the first total synthesis and reassignment of the relative stereochemistry of naturally occurring 16-hydroxy-16,22-dihydroapparicine. Our novel route proceeds by a cascade reaction to efficiently construct a 1-azabicyclo[4.2.2]decane core, along with two stereocenters (C-15 and C-16). The C-16 quaternary carbon was constructed through stereospecific 1,2-addition using an indole nucleophile to an aldehyde or a methylketone. The stereospecific synthesis of two diastereomers of the target product has revealed the true relative stereochemistry of the natural compound.