Synthesis of Menthol Glycinates and Their Potential as Cooling Agents

Abstract

A convenient method of synthesis has been developed for a new class of potential cooling agents, menthol glycinates. These compounds are prepared in two synthetic steps, starting from bromoacetyl bromide and (−)-menthol. The resulting brominated menthol ester readily undergoes substitution reactions with NH 3 and 1°or 2°amines to provide menthol glycinates. For most of the prepared compounds, the two-step synthetic procedure requires no aqueous phase extractions.

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

“…Menthol glycinates are considered as potential cooling agents while the conjugates of (−)‐menthol with other amino acids potential to be TRPM8 agonists is not reported earlier [14] . The synthesis of such conjugates of menthol with few amino acids is reported in the present work.…”

“…Menthol glycinates are considered as potential cooling agents while the conjugates of (À )-menthol with other amino acids potential to be TRPM8 agonists is not reported earlier. [14] The synthesis of such conjugates of menthol with few amino acids is reported in the present work. Klumpp et al, have reported the synthesis of a series of amine derived menthol glycinates and aniline derived menthol glycinates in moderate to good yields.…”

“…The synthesis of such conjugates of menthol with few amino acids is reported in the present work. Klumpp et al., have reported the synthesis of a series of amine derived menthol glycinates and aniline derived menthol glycinates in moderate to good yields [14,15] . In both these procedures, bromoacetyl bromide is used to link the substrates.…”

“…Klumpp et al, have reported the synthesis of a series of amine derived menthol glycinates and aniline derived menthol glycinates in moderate to good yields. [14,15] In both these procedures, bromoacetyl bromide is used to link the substrates. This reagent is noncompatible with oxidizing agents, corrosive and reacts violently with water.…”