Four-Carbon Chain Elongations

7 Four-Carbon Chain Elongations 13.5.7.1 But-2-en-l-yl Metal Additions 

A synthesis of (+)-KDO has been reported by Martin and Zinke [118], which relies on the highly stereoselective addition of 2-furyllithium to 2,3-O-isopropylidene-D-glyceraldehyde R)-24. 

SCHEME 13.65 Marshall s allylation applied to the synthesis of destomic acid. Copyright 2006 by Taylor Francis Group LLC 

SCHEME 13.69 Synthesis of a branched-chain amino aldonolactone. 

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The second procedure, Part B, Illustrates an easy synthesis of y-keto esters by "reductive succlnoylation" of a ketal function.5 It is useful not only for the preparation of keto esters, but also as a four-carbon chain-elongation reaction starting from ketones. The reaction is applicable to a diverse range of ketals as shown in Table II. The enol silyl ether... 

In some cases, acyl-CoA conjugates formed from xenobiotic acids can also enter the physiological pathways of fatty acids catabolism or anabolism. A few examples are known of xenobiotic alkanoic and arylalkanoic acids undergoing two-carbon chain elongation or two-, four- or even six-carbon chain shortening. In addition, intermediate metabolites of (3-oxidation may be seen, as illustrated in Figure 32.10 with valproic acid, whose acyl-CoA intermediate (22) is a substrate for some first steps of 3-oxidation. ... 

A review of the four reagent systems developed for direct C-H oxidation and establishing three carbon-chain elongations via straightforward installation of carbon unit to C-H bonds is published. Highly reactive chemical species acting like oxygen radical are utilized as a key C-H activator. ... 

This first round of elongation produces the four-carbon butyryl-ACP. The cycle now repeats with malonyl-ACP adding two-carbon units in each cycle to the lengthening acyl-ACP chain. This continues until the 16-carbon palmitoyl-ACP is formed. This molecule is not accepted by the acyl-malonyl-ACP condensing enzyme, and so cannot be elongated further by this process. Instead it is hydrolyzed by a thioesterase to give palmitate and ACP. 

The net effect of these eight steps is to take two acetyl groups and combine them into a single four-carbon butyryl group. Further condensation of butyryl synthase with another malonyl ACP yields a six-carbon unit, and still further repetitions of the pathway add two more carbon atoms to the chain each time until the 16-carbon palmitic acid is reached. Further chain elongation of palmitic acid occurs by reactions similar to those just described, but acetyl CoA itself rather than malonyl ACP is the two-carbon donor. 

Four enzymes participate in each iterative cycle of chain elongation (Fig. 3). The acetoacyl-ACP formed from the initiating FabH condensation is reduced by an NADPH-dependent P-ketoacyl-ACP reductase (fabG), and a water molecule is then removed by a P-hydroxyacyl-ACP dehydrase (fabA otfabZ). The last step is catalyzed by enoyl-ACP reductase (fabl or fabK) to form a saturated acyl-ACP, which serves as the substrate for another condensation reaction or when the chain length reaches 16-18 carbons is utilized for membrane phospholipid synthesis. p-Ketoacyl-ACP synthase I or II (fabB or fabF) initiates additional... 

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