An ammonia-triggered stereocontrolled conversion of a γ-lactone to the central tetrahydropyran of pederin, psymberin, and onnamides D-F

The onnamides, pederin, and psymberin have each attracted attention because of their potent biological activity and interesting structural features. A short (eight steps) and efficient stereocontrolled route to the central tetrahydropyran ring in these natural products has been developed from (S)-malic acid. The key sequence involves the conversion of a γ-lactone to a tetrahydropyran structure triggered by the addition of ammonia. A new approach to a tetrahydropyransubunit found in pederin, psymberin, and onnamides D-F is presented. The key sequence involves a ring expansion from a γ-lactone to a tetrahydropyran ring. Conditions for achieving both the kinetic and thermodynamic cyclization reactions have been developed, and models to explain the course of each are presented.