Synthesis and anticancer evaluation of new lupane triterpenoid derivatives containing various substituent at the 2 or 3 position

[Display omitted] •Modified in the A ring betulinic acid derivatives were synthesized.•Methodology to access 2α-(aminomethyl)betulinic acid derivatives has been achieved.•3α-Alkynylbetulinic acid derivatives by the reaction of lithium acetylides with betulonic acid ester.•Catalytic system composed of AuCl3–AgOTf induced the elimination reaction.•The anticancer activities were investigated against various tumor cell lines. Betulonic acid benzyl ester 1 has been subjected to a series of structural modifications for the purpose of new triterpenoid synthesis and evaluating for anticancer activity. The one-pot two step synthesis of 2α-(aminomethyl)betulinic acid benzyl ester derivatives 3a–f (yield 46–69 %) was achieved by the Mannich reaction of compound 1 with methyleneiminium salts, generated in situ from N,N-disubstituted bis(amino)methanes 2a–f by the action of acetyl chloride in dichloromethane, and subsequent reduction of aminomethylation products with sodium borohydride. Minor 2β-(aminomethyl) triterpenoids 4c,d,f were also isolated (yield 6–15 %). We found, that the stereoselective reaction of triterpenoid 1 with acetylides, generated at –78 °C from alkynes in the presence of n-BuLi, has been useful and noteworthy as the key step in providing of new alkyne substituted triterpenoids – benzyl 3-alkynyl-3-deoxy-2(3),20(29)-lupadiene-28-oates or 3-deoxy-2(3)-dehydro-28-oxoallobetulin derivative. The new compounds were examined for anticancer activity against the human cell lines (MTT assay). All tested derivatives were non-toxic on human fibroblasts. The 3‐(phenylethynyl)lupa-2(3),20(29)-diene 9 showed selective cytotoxicity on cervical cancer cell lines. Tumor cells death trigged by the most active compound 4f resulted from apoptotic processes. These data make the series of synthesized 2 or 3 substituted lupane derivatives as promising compounds with anticancer potential.