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

Alessia Caso; Alfonso Mangoni; Gennaro Piccialli; Valeria Costantino; Vincenzo Piccialli

doi:10.1021/acsomega.7b00095

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

ACS Omega. 2017 Apr 30;2(4):1477-1488. doi: 10.1021/acsomega.7b00095. Epub 2017 Apr 17.

Authors

Alessia Caso¹, Alfonso Mangoni¹, Gennaro Piccialli¹, Valeria Costantino¹, Vincenzo Piccialli²

Affiliations

¹ Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy.
² Department of Chemical Sciences, University of Naples Federico II, via Cintia 4, 80126 Naples, Italy.

Abstract

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.