Dehydration biological examples

Notice that the conversion of citrate to cis-aconitate is a biological example of the dehydration of an alcohol to produce an alkene (Section 13.5). The conversion of cis-aconitate to isocitrate is a biochemical example of the hydration of an alkene to produce an alcohol (Sections 12.5 and 13.5). 

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

As noted previously in Section 11.10, biological dehydrations are also common and usually occur by an ElcB mechanism on a substrate in which the -OH group is two carbons away from a carbonyl group. An example occurs in the biosynthesis of the aromatic amino acid tyrosine. A base first abstracts a proton from the carbon adjacent to the carbonyl group, and the anion intermediate... 

Another interesting class of five-membered aromatic heterocycles has recently been published by Tron et al. [54]. These compounds have biological activity in the nM range. An example of the formation of these furazan (1,2,5-oxadiazole) derivatives is shown in Scheme 9. The diol 50 was oxidized to the diketone 51 using TEMPO and sodium hypochlorite. Transformation to the bisoxime 52 was performed in an excess of hydroxylamine hydrochloride and pyridine at high temperature for several days. Basic dehydration of 52 formed two products (53a and b). A Mitsunobu reaction was then employed using toluene as solvent to form compound 53b in 24% yield. 

Peptides are short chains of amino acids linked by peptide bonds. Most biologically active peptides contain two to ten amino acids. Peptide bonds are formed between the carboxyl carbon of one amino acid and the amino nitrogen of another. Since water is released, this is an example of dehydration synthesis. The bond forms as illustrated in Figure 16.7. 

Table III summarizes the parameters that affect Brrfnsted acid-catalyzed surface reactions. The range of reaction conditions investigated varies widely, from extreme dehydration at high temperatures in studies on the use of clay minerals as industrial catalysts, to fully saturated at ambient temperatures. Table IV lists reactions that have been shown or suggested to be promoted by Br nsted acidity of clay mineral surfaces along with representative examples. Studies have been concerned with the hydrolysis of organophosphate pesticides (70-72), triazines (73), or chemicals which specifically probe neutral, acid-, and base-catalyzed hydrolysis (74). Other reactions have been studied in the context of diagenesis or catagenesis of biological markers (22-24) or of chemical synthesis using clays as the catalysts (34, 36). Mechanistic interpretations of such reactions can be found in the comprehensive review by Solomon and Hawthorne (37).

Notice that an acid catalyst is normally added for imine formation. Without an acid catalyst, the reaction is veiy slow, though in some cases it may still take place (oximes, for example, will form without acid catalysis, but form much faster with it). It s important to notice that acid is not needed for the addition step in the mechanism (indeed, protonation of the amine means that this step is very slow in strong acid), but is needed for the elimination of water later on in the reaction. Imine formation is in fact fastest at about pH 4-6 at lower pH, too much amine is protonated and the rate of the first step is slow above this pH the proton concentration is too low to allow protonation of the OH leaving group in the dehydration step, Imine formation is like a biological reaction it is fastest near neutrality. 

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