4-Oxothiazolidines with Exocyclic C=C Double Bond(s): Synthesis, Structure, Reactions and Biological Activity
Milovan Stojanovic, Zdravko Dzambaski, Bojan Bondzic, Jovana Aleksic and Marija Baranac-Stojanovic
Affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, P.O.Box 158, 11000 Belgrade, Serbia.
Keywords: 2-Alkylidene-4-oxothiazolidine, biological activity, heterocycle, push-pull alkene, reactivity, structure, synthesis.
4-Oxothiazolidine core, owing to the wide range of pharmacological activities exhibited by its derivatives, has been
recognized as an important structural motif in biologically active compounds. A subclass constitutes 4-oxothiazolidines with an exocyclic
C=C double bond at the C(2)-position. Some of these derivatives are registered as active substances for the treatment of various diseases,
such as Ralitoline, an antiepileptic, Etozolin, a diuretic, and Piprozolin, a choleretic. The exocyclic C=C double bond in these compounds
contains one or two electron-accepting groups at its other end, so that they also belong to the class of the so-called push-pull alkenes. In
the case of the nitrogen-unsubstituted molecules, the enamino tautomeric form with the exocyclic double bond is stabilized by the
extended electron delocalization arising from the push-pull effect. In the absence of push-pull effect, the imino form would dominate.
Therefore, these compounds exhibit properties characteristic for both 4-oxothiazolidine ring and push-pull alkenes. They are also proved
to be useful synthetic interamediates for the formation of various mono- and polyheterocycles. The importance of 4-oxothiazolidine
derivatives is witnessed by several review articles, the latest published in 2012, mainly dealing with the chemistry and biological activity
of various 2-imino, 2-oxo, 2-thioxo and 2-alkyl(aryl)-substituted compounds. The lack of a comprehensive review on 2-alkylidene-4-
oxothiazolidines has prompted us to collect the literature covering their synthesis, structure, reactivity and biological activity. Derivatives
with two exocyclic C=C double bonds are included, too.
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