0009-3122/14/5001-0065©2014 Springer Science+Business Media New York 65 Chemistry of Heterocyclic Compounds, Vol. 50, No. 1, April, 2014 (Russian Original Vol. 50, No. 1, January, 2014) SYNTHESIS OF TRITERPENE A-CONDENSED AZOLES N. V. Galaiko 1 , A. V. Nazarov 1 , I. A. Tolmacheva 1 , P. A. Slepukhin 2 , Yu. B. Vikharev 1 , O. A. Maiorova 1 , and V. V. Grishko 1 * Lupane and 18H-oleanane -hydroximino ketones were used to synthesize derivatives condensed at ring A with a substituted azole fragment, namely, C(2)–C(3)-fused oxazoles and 1,2,3-triazoles. Triterpene isoxazoles fused at the C(1)–C(2) bond are described for the first time. An optimized method was proposed for the synthesis of unsubstituted 1,2,3-triazoles, displaying cytotoxic activity (IC 50 8.4-40.7 M) relative to rhabdomyosarcoma, lung carcinoma, and MS melanoma cell lines. Keywords: allobetulone, betulonic acid, -hydroximino ketones, isoxazoles, oxazoles, 1,2,3-triazoles, cytotoxic activity. The availability, high synthetic potential, and highly pronounced biological activity of polycyclic plant triterpenoids have led to interest in this group of compounds as a valuable source of new therapeutic agents. Many examples of the chemical transformation of triterpenoids to give more active semisynthetic derivatives indicate the promise for derivatives obtained by introducing a heterocyclic fragment condensed with ring A of the triterpene skeleton. In particular, various lupane triterpenoids have been described with a C(2)–C(3)-fused heterocyclic fragment obtained from available derivatives of the pentacyclic triterpenoid, betulin [1-6]. We have discovered a single example in the literature for the preparation of a triterpenoid with a C(1)C(2)-fused pyrazine fragment [7]. In this case, triterpene oximes were used as starting compounds in addition to -bromo ketones, diosphenols, -ketoesters, and semicarbazones. For example, mono- and dioximated derivatives of betulone and allobetulone were used to obtain the corresponding pyrroles and oxadiazoles fused with ring A of the triterpene skeleton at the C(2)C(3) bond [8-10]. In the present work, we synthesized new heterocyclic derivatives starting from lupane and 18H-oleanane -hydroximino ketones, whose method of preparation from the methyl ester of betulonic acid and allobetulone was proposed in our previous work [11]. We note that the good prospects for using triterpene -hydroximino ketones in the synthesis of C(2)C(3)-fused heterocycles were recently confirmed in the preparation of derivatives of 1,2,5-oxadiazole and 2-methyloxazole from -hydroximino ketones obtained from betulin and oleanolic acid [10, 12]. _______ *To whom correspondence should be addressed, e-mail: grishvic@gmail.com. 1 Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences, 3 Akademik Korolev St., Perm 614013, Russia. 2 Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, 22 S. Kovalevskaya St. / 20 Akademicheskaya St., Yekaterinburg 620990, Russia, e-mail: slepukhin@ios.uran.ru. _________________________________________________________________________________________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 72-83, January, 2014. Original article submitted October 13, 2013.