Abstract: Based on the betulin with terpenoid as lead structure, the C-28 and C-29 of betulin were modified by the oxidants including the mixture of CrO₃ and TEMPO and the m-CPBA, and aldehyde groups were selectively introduced into C-28 and C-29 sites, respectively. The compounds were further oxidized to betulinic acid at C-28 and C-29 sites, respectively. Finally, four oxidized derivatives were obtained and characterized by ¹H NMR. The results showed that the yield of C-28 betulinaldehyde oxidized by the mixed oxidant of CrO₃ and TEMPO was increased to 36.98% compared with that oxidized by single oxidant. When m-CPBA was used as oxidant and acetone was used as solvent, the yield of C-29 betulinaldehyde was 39.06%,which was the highest compared with others. The inhibitory rate and IC₅₀ of betulin and its oxidized derivatives on the proliferation of two cell lines (HepG2 and A549) were measured by modified MTT method. The results showed that there was no significant difference in the antitumor activity between betulin and betulinaldehyde at the C-28 and C-29 sites. The antitumor activity of betulinic acid at C-28 and C-29 sites was significantly higher than that of betulin and betulinaldehyde at the same site. There was no significant difference in the toxicity of HepG2 and A549 cells between the oxide of betulin C-28 and C-29 sites.

Key words: betulin, betulinic acid, oxide, synthesis, antitumor