Synthesis Of Benzolactam-V8

In the recent years, the modulator of Protein Kinase C has always been an intresting focus to chemists due to its significant impact on the Alzheimer’s disease and cancer.(2S,5S)-5-(hydroxymethyl)-2-isopropyl-1-methyl-1,2,5,6-tetrahydrobenzo[e][1,4]diazocin-3(4H)-one (that is Benzolactam-V8, the very key core to the PKC modulator) was successfully optimized and synthesized by us.Herein, we studied and established the synthesis of Benzolactam-V8, which was prepared from L-2-nitro-phenylalanine as the starting material via easy reaction sequences: estification、protection、reduction and hydrogenation. Then the group of2-((2-((S)-2-((tert-but--oxycarbonyl)amino)-3-methylbutanoat was introduced as a chiral group via nucleophilic substitution, followed by condensation, ring-closed reaction and methylation. All the compounds were determinded by1H-NMR.In the first, we estabilished the new route of Benzolactam-V8’s synehsis, detailed the reaction optimization such as the improvements from reaction time、temperature、SMs’s equips、choice of catalyst. Then we afforded much more straightforward measure in their workup, about90%purity can be achieved in nearly most step. The overall yiled can be accepted at5folds than others before.Finally, the larger scale of Benzolactam-V8was successfully made in our kilo-lab which was a promising new idea and access to the GMP factory in the future.