The high content of betulin (up to 30%) in white birch bark and the ease of its isolation in almost any amount, make it important starting material for synthesis of new compounds with various interesting medical properties. Betulin (1) has three available sites for simple chemical modification, namely: secondary hydroxyl group at position C-3, primary hydroxyl group at position C-28 and isopropenyl side chain at position C-19 [1,2]. In the last few years a large number of betulin derivatives have been reported to possess anticancer, anti-inflammatory, anti-HIV and anti-leishmanial activity [2,3].

In this paper we present the synthesis of new series of derivatives of betulin containing one, two or three pharmacophores bearing an alkynyl function at the C-3, C-28 and/or C-30 positions. This interest has resulted from the recognition of the value of such compounds in a wide range of biological and chemical synthetic aspects. Synthesis of alkynyl derivatives of betulin (2) has been described in scheme presented below.

The structure of obtained compounds were determined on the basis of their spectroscopic and crystallographic data. All compounds were tested for cytotoxic activity against human: breast cancer (T47D), leukemia (CCRF/CEM), colorectal adenocarcinoma (SW707) and murine: leukemia (P388), (Balb3T3) cancer cell lines. The presented studies demonstrates that simple modification of the parent structure of betulin (1)  can produce new potentially interesting anti-cancer agents.  The presence of an alkynyl group offers the possibility for further functionalization of betulins (2) and construction of new heterocyclic systems.

References:

[1] Simonsen J., Ross W.C.J. The Terpenes, (1957) Cambridge University Press, New York,     vol V, p. 317-318.

[2] Alakurtti S., Mäkelä T., Koskimies S., Yli-Kauhaluoma J. Pharmacological properties of the ubiquitous natural product betulin. Eur. J. Pharm. Sci., 2006, 29, 1-13.

[3] Boryczka S., Bębenek E., Wietrzyk J., Kempińska K., Jastrzębska M., Kusz J., Nowak M. Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin. Molecules, 2013, 18, 4526-4543.

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