Scale-Up Synthesis of 1‑Methyladamantane and Its Functionalization as a Key Point for Promising Antiviral Agents

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.