Synthesis of α,β‐DI[3H]–2–fluoro–L–histidine

Abstract

AbstractThe potent antimetabolite, 2‐fluoro‐L‐histidine, has been synthesized from 2‐fluoroimidazole with nonexchangeable 3H labeling in the side chain. 2‐Fluoro‐4‐iodoimidazole was N‐tritylated, was subjected to metal‐halogen exchange with n‐butyllithium, and the carbanion formylated with DMF. The imidazole‐4‐aldehyde was condensed with hippuric acid, the azlactone was solvolyzed with methanol, and the trityl group was removed by selective reduction with PtS2. The resultinq 2‐fluoro‐α‐benzamidoacrylic ester was reduced with tritium gas and the blocking groups were removed successively with base and with acylase I to produce the L‐enantiomer of the free amino acid analogue.