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Synthesis 2006(23): 3979-3986  
DOI: 10.1055/s-2006-950327
PAPER
© Georg Thieme Verlag Stuttgart · New York

Reactions of Activated Lupane Oxo-Compounds with Diazomethane: An Approach to New Derivatives of Cytotoxic Triterpenes

Milan Urbana,, Jiri Klinota, Iva Tislerovaa, David Biedermanna, Marian Hajduchb, Ivana Cisarovac, Jan Sarek*a
a Dept. of Organic and Nuclear Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Prague 2, Czech Republic
Fax: +420(22)1951332; e-Mail: jan.sarek@gmail.com;
b Laboratory of Experimental Medicine, Department of Pediatrics, Faculty of Medicine, Palacký University and Faculty Hospital in Olomouc­, Puskinova 6, 77520 Olomouc, Czech Republic
c Dept. of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Prague 2, Czech Republic
Further Information

Publication History

Received 13 June 2006
Publication Date:
20 October 2006 (online)

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Abstract

The reactions of diazomethane with activated carbonyl derivatives of lupane were investigated. Previously known cytotoxic oxo-compounds were chosen as substrates, which allowed new information on the structure-activity relationships of this group of compounds to be obtained. Reactions of lupane derivatives containing an unsaturated aldehyde, α-diketones or 18,19-seco-triketones with diazomethane gave 1,3-dipolar and carbene addition products, for example oxirane and dihydropyrazole derivatives, along with products arising from homologation of cyclic ketones, such as methylenoleth­ers. We synthesised seventeen new compounds containing dihydropyrazole, oxirane, cyclopropane or 3-methoxycyclohex-2-en-1-one rings on the triterpenic skeleton. All compounds were tested for their in vitro cytotoxic activity against the T-lymphoblastic leukaemia CEM cell line.

Key words

addition reactions - antitumor agents - diazo compounds - ketones - terpenoids

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1

Current address: Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic, Flemingovo n. 2, 16610 Prague 6, Czech Republic.

20

CCDC 610293 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_reguest/cif or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk