An expedient route for the practical preparation of optically active (−)-gossypol

A simple and practical procedure has been developed for the resolution of racemic gossypol. The commercially available l-amino acid esters have been employed as the resolving agents with the l-tryptophan methyl ester (l-Trp-OMe) as the best reagent of choice. The individual diastereoisomeric gossypol adducts derived from l-Trp-OMe are readily separated by a simple filtration step to give the (−)-diastereoisomeric adduct, and its (+)-diastereoisomeric adduct can be easily obtained by simple evaporation of the mother liquor. Acid hydrolysis of the separated adduct gave (−)-gossypol and (+)-gossypol, respectively, in high chemical yields (quantitatively) and in high enantiomeric excesses (>95%).

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(Rg,S)-Gossypol-bis-(l-tryptophan methyl ester) schiff’s baseC54H54N4O10De = 95% (by NMR)[α]D19.7=-1091 (c 0.255, CHCl3)Source of chirality: synthesisAbsolute configuration: (Rg,S)

(Sg,S)-Gossypol-bis-(l-tryptophan methyl ester) schiff’s baseC54H54N4O10De >99% (by NMR)[α]D26=+288 (c 0.55, CH3OH)Source of chirality: synthesisAbsolute configuration: (Sg,S)

(R)-(−)-GossypolC30H30O8Ee = 94.7%[α]D24.7=-344.98 (c 0.1, CH3OH)Source of chirality: chemical resolution via l-amino acid esterAbsoulte configuration: (R)

(S)-(+)-GossypolC30H30O8Ee = 95.7%[α]D26=+364.9 (c 0.22, CH3OH)Source of chirality: chemical resolution via l-amino acid esterAbsolute configuration: (S)