Alcohols, acetylation oxidation

Much of the acetaldehyde formed from alcohol is oxidized in the liver in a reaction catalyzed by mitochondrial NAD-dependent aldehyde dehydrogenase (ALDH). The product of this reaction is acetate (Figure 23-1), which can be further metabolized to C02 and water, or used to form acetyl-CoA. 

The remaining three steps are accomplished without purification of the intermediate products. The secondary hydroxy group is protected by acetylation and the benzyl ether is removed by hydrogenolysis to provide a primary alcohol. The alcohol is oxidized to a carboxylic acid by ruthenium(III) chloride or pyridinium dichromate. This method has been applied to the synthesis of various enzyme inhibitors containing the 1-hydroxyethylene isostere. 

Fatty acid degradation and synthesis are relatively simple processes that are essentially the reverse of each other. The process of degradation converts an aliphatic compound into a set of activated acetyl units (acetyl CoA) that can be processed by the citric acid cycle (Figure 22.2). An activated fatty acid is oxidized to introduce a double bond the double bond is hydrated to introduce an oxygen the alcohol is oxidized to a ketone and, finally, the four carbon fragment is cleaved by coenzyme A to yield acetyl CoA and a fatty acid chain two carbons shorter. If the fatty acid has an even number of carbon atoms and is saturated, the process is simply repeated until the fatty acid is completely converted into acetyl CoA units. 

The conclusive proof that in acetone there are two methyl groups present is in the synthesis of acetone from acetic acid and acetyl chloride, reactions which we shall soon study. With this conclusive proof our formula, as we have written it, must be correct and our ideas in regard to the oxidation of compounds containing hydrogen linked to carbon are probably correct also. The steps in the oxidation are probably as we have indicated, viz., that hydrogen is first converted into hydroxyl and when as a result of such oxidation, two hydroxyls are linked to one carbon the compound loses water, leaving one oxygen doubly linked to the carbon. This enables us to understand the facts that only primary alcohols on oxidation yield aldehydes, secondary alcohols yield ketones, while tertiary alcohols yield neither aldehydes nor ketones. 

Dimethyl sulfoxide-Acetic anhydride [1, 305, after citation of ref. 43J. Albright and Goldman433 have reported further on the oxidation of secondary alcohols to ketones with DMSO-Ac20 at room temperature. In the case of yohimbine and the steroid secondary alcohols studied, oxidation apparently was faster than acetylation. The method is particularly useful for sterically hindered alcohols. The following mechanism is proposed ... 

Note that the dehydration of citrate takes place specifically away from the carbon atoms of the acetyl group that added to oxaloacetate in step 1. steps 3-4 Oxidative decarboxylations. Isocitrate, a secondary alcohol, is oxidized by NAD in step 3 to give a ketone, which loses C02 to give -ketoglutarate. Catalyzed by the enzyme isocitrate dehydrogenase, the decarboxylation is a typical reaction of a 0-keto acid, just like that in the acetoacetic ester synthesis (Section 22.8). 

Recall In fatty-acid degradation, we encounter coenzyme A, mitochondrial matrix, trans double bonds, L-alcohols, P-oxidation, NAD+ and FAD, acetyl-CoA, and separate enzymes. What are the counterparts in fatty-acid synthesis ... 

Finally, the etiojervane analogue of corticosterone (236) has been synthesized from jervine (231), through the known intermediate (232). The unsaturated a-hydroxy-ester (233) was prepared from (232) by a Darzens reaction, followed by boron trifluororide rearrangement. Selective catalytic hydrogenation and lithium aluminium hydride reduction gave a tetraol, isolated as its acetonide (234), which by oxidation at C-3 gave the ajS-unsaturated ketone (235). The last steps of the sequence, which involved modifications of the side-chain, entailed acid hydrolysis, acetylation of the primary alcohol, and oxidation at C-20 to give (236)." ... 

Rearrangement reactions of glycal derivatives continue to be of interest, trl- -acetyl-D-glucal giving the a-glycoside (7) under standard conditions with boron trifluorlde as catalyst and the appropriate alcohol. Periodate oxidation gave the o-vlnyl... 

The Dess-Martin periodinane ( DMP ) reagent, U,l-tris(acetyloxy)-l,l-dihydro-l,2-benziodoxol-3(l//)-one, has also been used in several complex syntheses for the oxidation of primary or secondary alcohols to aldehydes or ketones, respectively (e.g., M. Nakatsuka, 1990). It is prepared from 2-iodobenzoic add by oxidation with bromic add and acetylation (D.a Dess, 1983). 

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