Effects of Unsaturated Groups

Presumably the cyclopentyl rest fills, in an optimal manner, a hydrophobic pocket of the active site of the enzyme. The cyclopentyl group has also proven advantageous in replacing a gem-dimethyl in a series of inhibitors of acyl-CoA-cholesterol acyltransferase, which is an enzyme implied in the absorption of the alimentary cholesterol.  

The introduction of an unsaturated group (vinyl, ethynyl, allyl, etc.) in a drug molecule generally entails one or several of the following consequences.  

Existence of electronic effects the unsaturated rests behave as electron attractors through inductive effects. Furthermore, direct interactions of donor-acceptor type are possible thanks to the tt electron cloud surrounds present in multiple bonds. 

Possibility of existence of a geometrical isomery (e.g. cis-trans geometric isomery). 

Possibility of activation through conjugation the association of several unsaturated functions in conjugated position (dienes, enynes, enones, enolides, polyunsaturated derivatives) renders the corresponding molecules very reactive. It facilitates especially the addition of biological nucleophiles and notably of thiols. 

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Note that there are other types of protons not listed here that can fall into the same chemical shift ranges listed above. The above categories are simply the most common ones. Also, through-space ( anisotropic ) effects of unsaturated groups (C=C, 0=0, and aromatic rings) can change chemical shifts from the above categories in ways that depend on conformation. 

Carboxylic acids were introduced by the reaction of the polysilane(II) with carboxylic acid anhydrides in the presence of an amine. Table 2 shows the results. In order to examine the effect of unsaturated bonds and halides in the side chain on photolysis, double bonds or chloride groups were introduced with the carboxylic acid. Polysilanes(III) were also soluble in polar solvents and basic aqueous solution. The solubility in tetramethyl ammonium hydroxide aqueous solution(TMAH) depended strongly... 

Resonance always results in a different distribution of electron density. For example, if the first term on the left in Figure 5.3 were the actual structure of aniline, the two unshared electrons of nitrogen would reside entirely on that atom. Because the real structure is actually a hybrid that includes contributions from the other canonical forms shown, the electron density of the unshared pair is spread over the ring. This decrease in electron density at one position and the corresponding increase elsewhere is called the resonance effect. When steric inhibition is present, resonance may be reduced or prevented because the atoms are sterically forced out of planarity The resonance effect of a group operates only when the group is directly connected to an unsaturated system. 

Numerous additional tests to determine the effect of the carbon chain on the functional group were conducted using a homologous series. The effect of unsaturation is pronounced only in cases where the double bond is conjugated with the aldehydic functional group. For example, trans-2-hexenal ( ) had a AT value of 1.50 as compared to n-hexanal with a value of 0.93. The ease of electron delocalization in trans-2-hexenal, as shown below, increases the polarity of the molecule, hence its higher AT value. 

On the contrary, the arrangement is dominated by electronic effects because of 7r-7r-interactions between the axial 0-Al and the substituents of the ketone. Repulsive interactions that occur with r-systems of unsaturated groups such as phenyl, alkenyl or alkynyl make these groups large... 

Baker-Nathan effect. Effect originally observed in the reaction of p-substituted benzyl bromides with pyridine and other processes in which the observed rates are opposite to those predicted by the electron-releasing inductive effect of alkyl groups, i.e., CH3 > CH3CH2 > (CH3)2CH > C(CH3)3. To explain it, a type of electron delocalization involving 2 electrons was proposed, termed hyperconjugation, which manifests itself in systems in which a saturated carbon atom attached to an unsaturated carbon or one with an empty orbital bears at least one hydrogen atom. 

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