Studies toward the Synthesis of Smenamide A, an Antiproliferative Metabolite from Smenospongia aurea : Total Synthesis of ent -Smenamide A and 16- epi -Smenamide A.

A chiral pool protocol toward the synthesis of the smenamide family of natural products is described. Two stereoisomers of smenamide A, namely, ent -smenamide A and 16- epi -smenamide A were synthesized with a 2.6 and 2.5% overall yield, respectively. Their carboxylic acid moieties were assembled starting from S -citronellene via two Wittig reactions and a Grignard process. Its coupling with either ( S )- or ( R )-dolapyrrolidinone, synthesized from Boc-l-Phe and Boc-d-Phe, respectively, was accomplished by using the Andrus protocol. This work also established the previously unknown relative and absolute configurations of smenamide A.
Competing Interests: The authors declare no competing financial interest.