A New Synthetic Route for Preparation of Enantiomers of Gossypol and Apogossypol from Racemic Gossypol

Abstract

Gossypol (1) isolated from cotton seed has recently received the increasing attention because it possesses a wide range of biological activities, including anticancer [1-4], contraceptive [5], antiviral [6-8] or antimicrobial activities [9]. Due to hindered rotation about the 2,2 -binaphthyl bond, gossypol exhibits two optically active forms, R-or (–)-1 and S-or (+)-1. Research in both in vitro and in vivo showed that the (–)enantiomer is more potent than the (+)-enantiomer and the racemic mixture (1) [10]. It was also hypothesized the selective action at low doses of the (–)-gossypol and a nonselective action from higher doses of either enantiomer [10]. Regarding the mechanism of action, the (–)-gossypol targets Bcl-2, BclxL and Mcl-1 proteins with higher affinities than (+)-gossypol. It is now in clinical trials as an orally administered agent for the treatment of several types of human cancer [11]. However, the application of gossypol as a therapeutic agent was limited because of the presence of the aldehyde group in its structure, resulting a number of side effects [12]. Apogossypol (2) is a reduced product of gossypol (1). Preclinical in vivo data show that apogossypol (2) has superior efficacy and markedly reduced toxicity compared to gossypol (1) [13]. In addition, the evaluation of the single-dose pharmaA New Synthetic Route for Preparation of Enantiomers of Gossypol and Apogossypol from Racemic Gossypol