Scale-Up Synthesis of 1-Methyladamantane and Its Functionalization as a Key Point for Promising Antiviral Agents
Org. Process Res. Dev. 2023, 27, 3, 477–487
Methyladamantane and its derivatives are rare chemotypes for industrial and even wide research use. The proposed scalable and inexpensive approach to such compounds opens the door to further extensive study of biologically active derivatives based on this uncommon core. Optimized synthesis of the key precursor, the chiral (1S,3R,5R,7S)-3-methyl-5-phenyladamantane-1-carboxylic acid, showcases some significant innovations. The main one is very effective and cost-efficient stacked injections in preparative chiral chromatography and showed potential for enantioresolution of chiral cage compounds. Scaling the preparation of (1S,3R,5R,7S)-trans-N-(4-aminocyclohexyl)-3-methyl-5-phenyladamantane-1-carboxamide, which was recently shown to have notable activity against the Ebola virus, to multigram levels is an excellent example of our elaboration significance. It may push forward further biological investigation of this promising antiviral agent.