We synthesized esters of alpha-tocopherol (VE) with the aim to develop new pro-vitamins, easily reconverted by enzymes in the skin and able to release another active moiety such as an amino acid, in order to obtain a synergic effect. In particular, the attention was dedicated to the amino acids glycine and alanine and to pyroglutamic acid. The sensitivity of pro-vitamins to enzymatic hydrolysis was evaluated in vitro using porcine liver esterase. Permeation experiments were performed using rabbit ear skin, for the quantification of pro-vitamins and derived VE in the epidermis and dermis. The new derivatives synthesized, and in particular the glycine and alanine derivatives, accumulated in rabbit skin in a significant extent and originated substantial amounts of alpha-tocopherol. In comparison with the acetate derivative (VEAc), the amounts accumulated are comparable or higher. Moreover, the new derivatives, being more hydrophilic, allow the use of vehicles such as the mixture water/propylene glycol/ethanol widely employed for the preparation of creams and gels. Finally, the enzymatic metabolism of these new derivatives generates not only VE, but also components that can have a further advantageous action on skin.