1. Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan;2. Faculty of Pharmacy, Iwaki Meisei University, Iwaki, Fukushima 970-8551, Japan
Abstract:
Total synthesis of (−)- and (+)-petrosin was accomplished. Stereocontrolled construction of the quinolizidine ring was achieved through a diastereoselective Mannich reaction and an aza-Michael reaction. Head-to-tail dimerization was performed by assembly of the two monomers using Suzuki–Miyaura cross coupling and subsequent ring-closing metathesis to construct the 16-membered ring. Biological evaluation of synthetic (−)- and (+)-petrosin and its derivatives indicated that the bispiperidine structure was necessary for the inhibition of syncytium formation.