Asymmetric, Stereocontrolled Total Synthesis of Paraherquamide A

Paraherquamide A (1), a potent anthelmintic agent, isolated from various Penicillium species with activity against ivermectin-resistant intestinal parasites, has been synthesized. The synthesis of a key intermediate, the α-isoprenylated, β-substituted hydroxyproline derivative, exploited a highly diastereoselective intramolecular SN2′ cyclization as a key step. This procedure is the first asymmetric, stereocontrolled, total synthesis of 1.