Biomimetic synthesis

Corey's carbenium-mediated cyclization of an engineered linear polyene to provide a tetracyclic steroid ring system,[4] which built upon studies of cationic cyclizations of linear polyenes by the Albert Eschenmoser and Gilbert Stork,[5][6] and the extensive studies of the W.S.

The key step in Heathcock's synthetic route involves a cyclization of acyclic dialdehydes A or B to form proto-daphniphylline.

Both dialdehydes (A or B) have carbon skeletons analogous to squalene and can be synthesized from simple starting materials.

Treating A or B with a sequence of simple reagents containing potassium hydroxide, ammonia, and acetic acid led to the formation of proto-daphniphylline.

It was proposed in the original report that hydroxyldihydropyran intermediate C was first formed when the dialdehyde starting material (A) was treated with potassium hydroxide.