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Synthesis 2008(21): 3465-3472  
DOI: 10.1055/s-0028-1083181
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Extension of the Library of Biologically Active γ-Alkylidene Butenolides

Petr Nováka, Milan Pourb, Marcel Špulákb, Ivan Votrubac, Martin Kotora*a,c
a Department of Organic and Nuclear Chemistry and Centre for New Antivirals and Antineoplastics, Faculty of Science, Charles University, Hlavova 8, 128 43 Praha 2, Czech Republic
Fax: +420(2)21951326; e-Mail: kotora@natur.cuni.cz;
b Centre for New Antivirals and Antineoplastics, Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
c Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Praha 6, Czech Republic
Further Information

Publication History

Received 23 June 2008
Publication Date:
16 October 2008 (online)

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Abstract

γ-Alkylidene butenolides bearing a deoxyriboside, a steroid, and a metallocene moiety were synthesized by stereoselective sequential cross-coupling lactonization procedure from the corresponding functionalized terminal alkynes with 3-iodopropenoic acids­. The high selectivity of the butenolide ring formation was secured by the Pd/Cu salt ratio. The resulting compounds were tested for antifungal and cytostatic properties. Most notably, γ-alkylidene butenolides bearing deoxyriboside moiety showed promising cytostatic activity in the micromolar range.

Key words

cross-coupling - lactones - catalysis - antitumor agents - palladium

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