The first total synthesis of paraherquamide A, a potent anthelmintic agent isolated from various Penicillium sp. with promising activity against drug-resistant intestinal parasites, is reported. Key steps in this asymmetric, stereocontrolled total synthesis include a new enantioselective synthesis of alpha-alkylated-beta-hydroxyproline derivatives to access the substituted proline nucleus and a highly diastereoselective intramolecular S(N)2' cyclization to generate the core bicyclo[2.2.2]diazaoctane ring system.