Betulin [lup-20(29)-en-3b,28-diol] is an abundant naturally occurring pentacyclic triterpene type lupane. Large quantities of it are in the external part of birch bark (content 25 – 30 %), from where it was separated in 1788 by Lovitz by sublimation, as one of the first natural products isolated from plants. Betulin and its derivatives have a wide spectrum of biological activities such as anticancer, antibacterial, antiviral, antiinflammatory, hepatoprotective and others [1]. The structure of betulin 1 (R=OH, R’=CH₂OH) has two hydroxyl groups: secondary at C-3, primary at C-28 and isopropylidene moiety at position C-19, where chemical modifications can be easily performed to yield new compounds, which possess various interesting pharmacological properties. So for only little attention has been paid to betulin derivatives containing alkyne groups [2, 3].

As an extension of our work on the development of anticancer agents, we synthesized the series of new derivatives of betulin 2 possessing one or two acetylenic functions. Betulin was isolated from the birch bark and then was oxidized to betulonic acid (R= O=, R’=COOH) and betulinic acid (R=OH. R’=COOH). Compounds 1 in the reactions with acetylenecarboxylic acids or acetylenehalides were converted into the corresponding mono- and diesters or ether derivatives 2.

The obtained compounds were tested for their anticancer activity in vitro against the cells of human and murine cancer cell lines.

[1] T.G.Tolstikova, I.V.Sorokina, G.A. Tolstikov, O.B.Flekhter, Russ.J.Bioorg.Chem., 32 (2006) 37-49.

[2] Y.Bi, J.Xu, X.Wu, W.Ye, S.Yuan, L.Zhang, Bioorg.Med.Chem.Lett., 17 (2007) 1475-1478.                                    

[3] S.F.Vasilevsky, A.I.Govdi, E.E.Shults, M.M.Shakirov, I.V.Sorokina, T.G.Tolstikova, D.S.Baev, G.A.Tolstikov, I.V.Alabugin, Bioorg.Med.Chem., 17 (2009) 5164-5169.

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