Applications of the vinylogy principle

Although numerous applications of the vinylogy concept are found in the medicinal chemistry literature, only a very few of them are of practical interest, mainly because the preparation of vinylogues usually leads to compounds which are more sensitive to metabolic degradation and more toxic (reactivity of the conjugated double bond) than the parent drug, without being more active. 

FIGURE 14.19 Formylacetone (enolic fwm) and vitamin C are comparable in acidity to carboxylic acids. 

CHAPTER 14 Molecular Variations in Homologous Series Vinylogues and Benzologues 

Catechol 0-methyltransferase inhibition represents therefore a valuable adjuvant to the 1-DOPA decarboxylase inhibition. Unfortunately, tolcapone exhibited severe liver damages and had to be removed from the market. The corresponding vinylogue entacapone is devoided of these side effects.  

For such compounds several possible isomeric and tautomeric forms can be considered. These include the (E) and (Z) geometrical isomers (a and b), as well as the tautomers nitrone (c), 5-hydroxy-isoxazolidine (d), and oxazirid-ine (e). Examination of the and NMR spectfa of the 

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FIGURE 14.31 Application of the vinylogy principle to the design of a fenbendazole bioisostere. ... 

Dienamine is a recent extension of the enamine concept to extended donors by using the principle of vinylogy. By extension of the enamine to conjugated dienamine starting from alkyl substituted enals or enones, it allows for the functionalization of a,p-unsaturated carbonyls in a- or 7-position using various electrophiles (Scheme 11.26). This potential of amine catalysts to promote extended functionalization is highly interesting, but because of its relative infancy, few synthetic applications of such activation have been reported to date. 

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