Stereoselective synthesis of [11 β-3H]prostaglandin E1

This report describes an efficient stereoselective synthesis of [11β‐3H]prostaglandin E1 ([11β‐3H]PGE1). The key multiply protected 11‐keto intermediate was prepared in only three steps from PGE1. Reduction of the ketone function at C‐11 with sodium borodeuteride and sodium borotritide, followed by sequential removal of protecting groups, afforded PGE1 labeled with deuterium and tritium, respectively, at the 11‐beta position. The reduction and deprotection were accomplished in one reaction flask without requiring purification of intermediates. Trace amounts of C11‐epimer formed in the reduction were readily separated by means of preparative reversed‐phase HPLC. Using sodium borotritide of nominally 67 Ci/mmol, we obtained [11β‐3H]PGE1 with specific activity of 15 Ci/mmol. A disposition study in the monkey with intravenous administration of this material indicated excellent in vivo metabolic stability of the 11β‐tritium label.