A Feasible Synthesis of (−)‐Menthol‐Amino Acid Conjugates as Potential TRPM8 Agonists

Abstract A simple and feasible protocol for synthesizing the menthol‐amino acid conjugates by reacting t ‐Boc‐amino acids with (1 R ,2 S ,5 R )‐(−)‐menthol is reported. The synthesis involved the formation of an ester bond between the protected amino acid and (−)‐menthol using DCC, and DMAP as reagents. The t ‐Boc‐menthol conjugates are deprotected using TFA in DCM to afford the menthol‐amino acid conjugates in excellent yield (>85 %). (−)‐Menthol possesses therapeutic properties, while amino acids are known for their diverse chemical functionalities and biological activities, making them a promising platform for designing TRPM8 agonists. By combining the unique characteristics of (−)‐menthol and amino acids, this conjugation approach can enhance TRPM8 agonistic activity. The synthesized conjugates are characterized through various spectroscopic techniques.