Preparation and in vivo evaluation of a water-soluble prodrug for 2R-gamma-tocotrienol and as a two-step prodrug for 2,7,8-trimethyl-2S-(beta-carboxyethyl)-6-hydroxychroman (S-gamma-CEHC) in rat.

2R-gamma-Tocotrienol (gamma-T3) is currently receiving attention because it has beneficial effects not observed with alpha-tocopherol. To achieve the effective delivery of gamma-T3, we synthesized three kinds of ester derivatives of gamma-T3 and evaluated their use as hydrophilic prodrugs for gamma-T3 in vitro and in vivo. 2R-gamma-Tocotrienyl N,N-dimethylamino-acetate hydrochloride (compound 3) was a solid compound, with high solubility and stability in water, and was converted to gamma-T3 by esterases in rat and human liver.