Asymmetric Total Synthesis of Both C14 Epimers of Petromyzestrosterol Enables Stereochemical Assignment and Olfactory Activity Evaluation in Sea Lamprey.

We achieved the first asymmetric total synthesis of petromyzestrosterol and its C14-epimer, clarifying their previously unresolved C14 stereochemistry and olfactory potency in sea lamprey. The route features assembly of the estrogenic skeleton via a Mizoroki-Heck reaction and Friedel-Crafts-type cyclodehydration, followed by a concise one-pot sequence of four reductive transformations. NMR comparison established a C14α-hydroxy configuration for petromyzestrosterol, and electro-olfactogram recordings demonstrated the natural 14α-isomer is significantly more potent than the 14β-isomer.