Synthetic Exploration Of3-bromopyruvic Acid Prodrug Activated By FAP-alpha

Objectives：To Design and explore the synthesis of3-bromopyruvic acid prodrug activated byFAP-alpha，in the purpose of finding antitumor prodrug with the advantages of better targeting,higher activity and better bioavailability.Methods:1. Z-Gly-Pro-NH2was synthesized from Z-Gly-OH and L-Pro-NH2. Then it reacted withpyruvic acid followed bromination. The targeted compound had thought to be synthesizedtherefore; Z-Gly-Pro-OtBu was synthesized from Z-Gly-OH and L-Pro-OtBu. Z-Gly-Pro-OHwas prepared from it through de-protection. Then Z-Gly-Pro-OH reacted with hydrazinehydrate to produce Z-Gly-Pro-NH-NH₂, Which reacted with pyruvic acid followed bromination.The targeted compound had thought to be synthesized therefore.2. All the compounds were identified by¹H NMR,¹³C NMR and ESI-MS.Results:1. Compound1、3、5、6、7、8、10、11were synthesized via different synthesis routes, but thetargeted compounds were not obtained.2. Compound10and compound11were unexpected. The reaction mechanism was concludedreasonably, and then we conducted a series of experiments to validate the conclusion.Conclusion:The synthesis of targeted compounds was explored via2different routes separately. Eightintermediate compounds were obtained,2of which were unexpected, and the reactionmechanism was concluded reasonably.