Scheme 1.

Methods of synthesis of betulinic acid [47,48,49,50,51,52]. Reagents and conditions: (i) chromium(VI) oxide; sulfuric acid, and acetone, H₂O; (ii) sodium tetrahydroborate and isopropyl alcohol; (iii) 4-acetylamino-2,2,6,6-tetramethylpiperidine-N-oxyl, sodium chlorite, tetrabutylammomium bromide, sodium hypochlorite, and phosphate buffer at 50 °C; (iv) 4-acetylamino-2,2,6,6-tetramethylpiperidine-N-oxyl, tetrabutylammomium bromide, sodium hypochlorite, and phosphate buffer (pH = 7.6) at 50 °C; (v) BAIB, TEMPO, NaH₂PO₄, NaClO₂, 2-methyl-2-butene, BuOAc, water, and t-BuOH at 20 °C for 6 h; (vi) 2,6,6-tetramethyl piperidine-N-oxyl, tetrabutylammomium bromide, and sodium hypochlorite in phosphate buffer with dichloromethane for 6 h with pH = 6.8; (vii) sodium dihydrogenphosphate, sodium permanganate, DCM, water, and tert-butyl alcohol at 25 °C for 3 h; (viii) K₂CO₃ and MeOH for 24 h; and (ix) KOH and MeOH with heating for 3 h.