Collect. Czech. Chem. Commun.
1985, 50, 2760-2774
https://doi.org/10.1135/cccc19852760
Preparation of 3-carboxypropanoates of digitoxin and digoxin and their conjugates with L-tyrosine
Pavel Drašara, Vladimír Pouzara, Ivan Černýa, Miroslav Havela, František Turečekb, Daniela Schmiedovác and Karel Verešc
a Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6
b The J. Heyrovský Institute of Physical Chemistry and Electrochemistry, Czechoslovak Academy of Sciences, 121 38 Prague 2
c Institute of Nuclear Biology and Radiochemistry, 142 40 Prague 4
Abstract
Digitoxin and digoxin 4'''-(3-carboxypropanoates)(4'''-hemisuccinates) III and X were prepared by an indirect method, using dicyclohexylcarbodiimide-induced condensation of the cardioglycoside with 4-(2,2,2-trichloroethoxy)-4-oxobutanoic acid in dichloromethane in the presence of 4-dimethylaminopyridine or pyridine followed by removal of the 2,2,2-trichloroethyl group with zinc in a mixture of tetrahydrofuran, acetic acid and water. The hemisuccinates III and X were condensed with L-tyrosine methyl ester in tetrahydrofuran, using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. Structure of the products was proved by 1H NMR and 13C NMR spectra. The conjugates IV and XI were labelled with [125I] in the L-tyrosine moiety. The obtained radioligands V and XII are designed as a part of the RIA system for cardioglycoside analyses.
