Three-Carbon Chain Elongations

6 Three-Carbon Chain Elongations 13.5.6.1 Allylmetal Additions 

SCHEME 13.59 Roush s conversion of D-glyceraldehyde into D-glucitol derivatives. 

Oxidation with TEMPO gives a-hydroxy-aldehydes 173 that are hydrogenated to 174. Chromatographic separation, followed by desilylation, provides enantiomerically pure 1,3-dideoxynojirimycin (-f)-175 [108]. 

3-deoxy-D-n7 (9-hexose. If aldol 179 is treated first with an equimolar amount of aluminium triisopropoxide, diol 182 is obtained in 62% yield (together with 15% of 181). Compound 182 is then converted into 3-deoxy-D-araZ m6 -hexose [111]. 

SCHEME 13.62 Conversion of D-glyceraldehyde into 3-deoxy-D-hexoses. Copyright 2006 by Taylor Francis Group LLC 

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Roush s three-carbon chain-elongation method applied to 2,3-O-cyclohexylidene-D-glyceralde-hyde (R)-62 is an efficient approach to D-glucitol derivatives, which relies on the vyfx-selective epoxidation of homoallylic alcohol 170 (Scheme 13.59) [105,107]. 

Other Methods of Three-Carbon Chain Elongation of Aldoses and Derivatives. . 905... 

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. ... 

Several s)uitheses of aminodeoxypentoses have employed a similar approach in which a three-carbon starting material is condensed with a two-carbon entity [237]. A synthetic equivalent of the glycoaldehyde anion, the dioxaborole 98 (O Scheme 46) has been used for the carbon chain elongation of aldehydes. Thus L-ribose is prepared from the addition of... 

The Michael addition represents an extremely efficient synthetic method for achieving chain elongation by adding a three (or more) carbon fragment electrophile to a nucleophilic moiety. Notice that the typical Michael electrophiles (e.g. 90) are products of condensation of carbonyl compounds and can be easily formed via the aldol-like condensation, the Wittig reaction (with ylides like 81), the Perkin reaction, or the Mannich reaction (see below). 

In addition to chain elongation, fatty acids are modified by the introduction of double bonds (desaturation). Enz5maes, called desaturases, catalyze the synthesis of unsaturated fatty acids. They can use saturated or partially unsaturated fatty acids as substrates. A -Desaturase, for example, catalyzes the introduction of a double bond between carbons 9 and 10 of a fatty acid (covmting from the carboxylic acid end). Three examples of reactions of A-desaturases are shown in Figiue 9.95. 

The growing fatty acid chain on the fatty acid synthase complex is elongated, two carbons at a time, by the addition of the three-carbon compound, malonyl CoA, which is subsequently decarboxylated. With each two-carbon addition, the growing chain, which initially contains a P-keto group, is reduced in a series of steps that require NADPH. NADPH is produced by the pentose phosphate pathway and by the reaction catalyzed by the malic enzyme. 

This reaction constitutes a method for the transformation of saturated cyclic or acyclic carbonyl compounds in three steps (silyl enol ether formation, halocarbene addition, rearrangement) to a,) -unsaturated carbonyl compounds with one-carbon ring enlargement or chain elongation, respectively. The rearrangement can be induced under acidic, basic, or thermolytic conditions, or with silver(I) salts. 

Fig. 1. Three biosynthetic pathways for major polyunsaturated fatty acids in mammals (desaturation, chain-elongation and chain-shortening steps). The site of desaturase action is shown by A9, A6, or A5. The major polyunsaturated fatty acids found in tissue lipids are linoleic (LA), arachidonic (ARA), docosapentaenoic (DPA), a-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Fatty acids are designated by the carbon chains the number of double bonds, and the position of the first double bond from the methyl terminus, as n-9, n-7, n-6, or n-3. Typical foods enriched with the indicated fatty acids are also shown.

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