Biological reaction, alcohol dehydration

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. 

A third important reaction of alcohols, both in the laboratory and in biological pathways, is their dehydration to give alkenes. The C-0 bond and a neighboring C—H are broken, and an alkene tt bond is formed. 

The synthesis of 6a-methyldigitoxigenin acetate (394) has been reported according to Scheme 19.198 Pregn-4-en-21-ol-3,20-dione was converted into its 6a-methyl derivative (387) using a previously described five-step reaction sequence biological hydroxylation furnished the 14a,12-diol (388) and reduction of the derived 21-acetate gave the 5/3-dihydro-steroid (389). Dehydration furnished the A14-olefin (390) which was converted into the 21-mesylate and thence into the lactone (391) by reaction with the monoethyl ester of malonic acid. The crude lactone was decarbox-ylated, reduced to the 3/3-alcohol (392), and converted into the bromohydrin (393) via its 3/3-acetate and thence by debromination into 6a-methyldigitoxigen 3-acetate... 

In biological systems the hydroxyl group is often involved in a variety of reactions such as oxidation, reduction, hydration, and dehydration. In glycolysis (a metabolic pathway by which glucose is degraded and energy is harvested in the form of ATP), several steps center on the reactivity of the hydroxyl group. The majority of the consumable alcohol in the world (ethanol) is produced by fermentation reactions carried out by yeasts. 

Oxidation of the resulting 3,5,17-triol, 24-5, leads to conversion of the only secondary alcohol in this intermediate to a ketone (Scheme 6.25). This intermediate readily dehydrates to form the conjugated ketone present in most biologically active steroids (25-1). Treatment with chloranil then extends the conjugated ketone by a new double bond in ring B. The 17-acetate, 25-2, formed by reaction with acetic anhydride under forcing conditions, is a potent progestin. 

A third important reaction of alcohols, both in the laboratory and in biological pathways, is their dehydration to give alkenes. Because of the usefulness of the reaction, a number of ways have been devised for carrying out dehydrations. One method that works particularly well for tertiary alcohols is the acidaqueous sulfuric acid in a solvent such as tetrahydrofuran results in loss of water and formation of 1-methylcyclohexene. 

Treatment of phenol with 1,2-diols and excess of cyclopentene (Sequiv.) in the presence of a well-defined cationic ruthenium hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1 mol%) in toluene at 100 C for 8-12h led to the formation of benzofuran derivatives (Eq. (7.18)) [24]. The catalytic C-H couphng method exhibited a broad substrate scope, tolerated carbonyl and amine functional groups, obviated the use of any expensive and often toxic metal oxidants, and liberated water as the only by-product. Furthermore, excellent regioselective addition of the linear 1,2-diols were observed, which yielded the -substituted benzofuran products exclusively. Such dehydrative C—H alkenylation and annulation reactions could be applied for a number of functionalized phenol and alcohol substrates of biological importance. 

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