Chain shortening

Alkyl radicals, R, react very rapidly with O2 to form alkylperoxy radicals. H reacts to form the hydroperoxy radical HO2. Alkoxy radicals, RO, react with O2 to form HO2 and R CHO, where R contains one less carbon. This formation of an aldehyde from an alkoxy radical ultimately leads to the process of hydrocarbon chain shortening or clipping upon subsequent reaction of the aldehyde. This aldehyde can undergo photodecomposition forming R, H, and CO or, after OH attack, forming CH(0)00, the peroxyacyi radical. 

When an a-hydroxy amide is treated with Br2 in aqueous NaOH under Hofmann rearrangement conditions, loss of C02 occurs and a chain-shortened aldehyde is formed. Propose a mechanism. 

Conversion of the aldehyde into a nitrile is accomplished by treatment of an aldose with hydroxvlamine to give an oxime (Section 19.8), followed by dehydration of the oxJme with acetic anhydride. The Wohl degradation does not give particularly high yields of chain-shortened aldoses, but the reaction is general for all aldopentoses and aldohexoses. For example, D-galactose is converted by Wohl degradation into n-lyxose. 

Much of the chemistry of monosaccharides is the familiar chemistry of alcohols and aldehydes/ketones. Thus, the hydroxyl groups of carbohydrates form esters and ethers. The carbonyl group of a monosaccharide can be reduced with NaBH4 to form an alditol, oxidized with aqueous Br2 to form an aldonic acid, oxidized with HNO3 to form an aldaric acid, oxidized enzymatically to form a uronic acid, or treated with an alcohol in the presence of acid to form a glycoside. Monosaccharides can also be chain-lengthened by the multistep Kiliani-Fischer synthesis and can be chain-shortened by the Wohl degradation. 

The general idea of peptide sequencing by Edman degradation is to cleave one amino acid at a time from an end of the peptide chain. That terminal amino acid is then separated and identified, and the cleavage reactions are repeated on the chain-shortened peptide until the entire peptide sequence is known. Automated protein sequencers are available that allow as many as 50 repetitive sequencing cycles to be carried out before a buildup of unwanted by products interferes with the results. So efficient are these instruments that sequence information can be obtained from as little as 1 to 5 picomoles of sample—less than 0.1 /xg. 

The four steps of the /3-oxidation pathway, resulting in the cleavage of an acetyl group from the end of the fatty-acid chain. The key chain-shortening step is a retro-Claisen reaction of a /3-keto thioester. Individual steps are explained in the text. 

Q Nucleophilic addition of coenzyme A to the keto group occurs, followed by a retro-Claisen condensation reaction. The products are acetyl CoA and a chain-shortened fatty acyl CoA. 

The retro-Claisen reaction occurs by initial nucleophilic addition of a cysteine -SH group on the enzyme to the keto group of the /3-ketoacyl CoA to yield an alkoxide ion intermediate. Cleavage of the C2-C3 bond then follows, with expulsion of an acetyl CoA enolate ion. Protonation of the enolate ion gives acetyl CoA, and the enzyme-bound acyl group undergoes nucleophilic acyl substitution by reaction with a molecule of coenzyme A. The chain-shortened acyl CoA that results then enters another round of tire /3-oxidation pathway for further degradation. 

The situation with some forms of biological deterioration is somewhat different. Where the agent is macrobiological, as in the case of rodents, insects, and marine borers, the attack is physical in nature, such as by gnawing or boring. The attack is not at the atomic or molecular level. Any breaking of molecular bonds such as in polymer chain shortening is thus accidental. The attack may be said to be at the material s structural level, not the polymer molecule level. 

The carbon chains of samrated fatty acids form a zigzag pattern when extended, as at low temperamres. At higher temperatures, some bonds rotate, causing chain shortening, which explains why biomembranes become thinner with increases in temperamre. A type of geometric isomerism occurs in unsaturated fatty acids, depending on the orientation of atoms or groups around the axes of double bonds, which do not allow rotation. If the acyl chains are on the same side of the bond, it is cis-, as in oleic acid if on opposite sides, it is tram-, as in elaidic acid, the tram isomer of oleic acid (Fig-... 

Fig.i General biosynthetic pathways for the production of alcohol, aldehyde, and acetate ester pheromone components in female moths. Top production of saturated fatty acids. Middle production of monounsaturated fatty acids and limited chain shortening produces intermediate compounds that can be reduced to an alcohol. Aldehyde and acetate ester pheromones are produced by an oxidase and acetyl-transferase, respectively. Bottom biosynthetic pathway for the production of the acetate ester pheromone components in the cabbage looper moth, Trichoplusia ni. The CoA derivatives are reduced and acetylated to form the acetate esters. Additional pheromone components include 12 OAc and ll-12 OAc... 

The chain shortening pathway has not been characterized in detail at the enzymatic level in insects. It presumably is similar to the characterized pathway as it occurs in vertebrates. These enzymes are a partial P-oxidation pathway located in peroxisomes [29]. The key enzymes involved are an acyl-CoA oxidase (a multifunctional protein containing enoyl-CoA hydratase and 3-hy-droxyacyl-CoA dehydrogenase activities) and a 3-oxoacyl-CoA thiolase [30]. These enzymes act in concert to chain shorten acyl-CoAs by removing an acetyl group. A considerable amount of evidence in a number of moths has accumulated to indicate that limited chain shortening occurs in a variety of pheromone biosynthetic pathways. 

Fig. 2 Action of desaturases and limited chain shortening can produce a variety of mono-unsaturated acyl-CoA precursors that can be modified to form unsaturated pheromone compounds. The arrow pointing down indicates limited chain shortening by two carbons. Modification of all 16-, 14-, 12-, and 10-carbon acyl-CoA derivatives on the carbonyl carbon can account for the majority of monounsaturated acetate esters, aldehydes, and alcohols identified as sex pheromones...

The above three examples illustrate how a species-specific pheromone blend is produced by the concerted action of desaturases, chain shortening enzymes, a reductase, and an acetyltransferase. The specificity inherent in certain enzymes in the pathway produces the final blend of pheromone components. 

Macrolide aggregation pheromones produced by male cucujid beetles are derived from fatty acids. Feeding experiments with labeled oleic, linoleic, and palmitic acids indicate incorporation into the macrolide pheromone component [ 117 ]. The biosynthesis of another group of beetle pheromones, the lactones, involves fatty acid biosynthetic pathways. Japonilure and buibuilactone biosynthesized by the female scarab, Anomalajaponica, involves A9 desaturation of 16 and 18 carbon fatty acids to produce Z9-16 CoA and Z9-18 CoA,hydroxylation at carbon 8 followed by two rounds of limited chain shortening and cyclization to the lactone [118]. The hydroxylation step appears to be stereospecific [118]. 

FIGURE 3 Pheromone biosynthetic pathways commonly used in moth sex pheromone glands to produce precursors for specific blends of acetates, alcohols, or aldehydes. Cascades of precursors are produced by combinations of unique A- -desaturases and limited chain-shortening steps. The six precursors for the cabbage looper blend (Figure 2) are in boldface type. 

In contrast to pheromones that involve single complex compounds, many moth species have been found to utilize a specific blend of relatively simple fatty acid-derived compounds. It appears that the evolution of a unique enzyme, A1 desaturase, used in combination with 2-carbon chain-shortening reactions (Figure 3) has allowed moth species to produce a variety of unsaturated acetates, aldehydes, and alcohols that can be combined in almost unlimited blends to impart species specificity. For example, biosynthetic precursors for the six-component pheromone blend of acetates for the cabbage looper moth (12) (Figure 2) can be determined easily from the cascade of acyl intermediates produced by the A11-desaturase and chain-shortening reactions (Figure 3). 

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