Dihydroxy acids

Recent developments tend to focus on the asymmetric aspects of stereoselective aldols but the diastereoselectivity is just as important. The cyclic ester 56 must of course form an E enolate and when the boron enolate -57 reacts with aldehydes the an//-aldol products 58 are formed with good stereoselectivity ranging from 4 1 to >20 1. The predominate isomer is that expected from the Zimmerman-Traxler transition state. The two benzylic-0 bonds can be cleaved by hydrogenation and the 2,3-dihydroxy acids anti-59 released in good yield.17... 

Reactions in which a product remains in the him (as above) are complicated by the fact that the areas of reactant and product are not additive, that is, a nonideal mixed him is formed. Thus Gilby and Alexander [310], in some further studies of the oxidation of unsaturated acids on permanganate substrates, found that mixed hlms of unsaturated acid and dihydroxy acid (the immediate oxidation product) were indeed far from ideal. They were, however, able to ht their data for oleic and erucic acids fairly well by taking into account the separately determined departures from ideality in the mixed hlms. 

Pantothenic acid, sometimes called vitamin B3, is a vitamin that makes up one part of a complex coenzyme called coenzyme A (CoA) (Figure 18.23). Pantothenic acid is also a constituent of acyl carrier proteins. Coenzyme A consists of 3, 5 -adenosine bisphosphate joined to 4-phosphopantetheine in a phosphoric anhydride linkage. Phosphopantetheine in turn consists of three parts /3-mercaptoethylamine linked to /3-alanine, which makes an amide bond with a branched-chain dihydroxy acid. As was the case for the nicotinamide and flavin coenzymes, the adenine nucleotide moiety of CoA acts as a recognition site, increasing the affinity and specificity of CoA binding to its enzymes. 

Reduction of the thioester group by 2 equivalents of NADPH gives (ft)-mevalonate, a dihydroxy acid. 

Lastly, it is worth mentioning the case of the dihydroxy-acid dehydratase from spinach, in which the reduced form of a [2Fe-2S] center was found to exhibit a heterogeneous EPR spectrum of the gav === 1-91 type, indicating the presence of noncysteinyl ligands at the reducible site. This signal was converted into a gav 1-96 type spectrum upon addition of the substrate, which suggests that this center may be involved in the catalytic cycle 264). 

Hydroxy C28 Dihydroxy acids S Fraxinus excelsior bark 0.9... 

This method, which utilizes 2-keto-3,4-dihydroxy acids or esters, is by far the best method for the preparation of ascorbic acids but it is dependent upon a successful process for the production of the 2-keto... 

The original preparation of y-crotonolactone by Lespieau involved a five-step sequence from epichlorohydrin and sodium cyanide. A recent detailed study of this procedure reported an overall yield of 25% for the lactone. Glattfeld used a shorter route from glycerol chlorohydrin and sodium cyanide hydrolysis and distillation of the intermediate dihydroxy acid yielded y-cro-tonolactone in 23% yield and -hydroxy-y-butyrolactone in 28% yield. The formation of y-crotonolactone in 15% yield has also been reported from pyrolysis of 2,5-diacetoxy-2,5-dihydrofuran at 480-500 . ... 

In plants a-dioxygenases (Chapter 18) convert free fatty acids into 2(R)-hydroperoxy derivatives (Eq. 7-3, step d).32a These may be decarboxylated to fatty aldehydes (step e, see also Eq. 15-36) but may also give rise to a variety of other products. Compounds arising from linoleic and linolenic acids are numerous and include epoxides, epoxy alcohols, dihydroxy acids, short-chain aldehydes, divinyl ethers, and jasmonic acid (Eq. 21-18).32a... 

The second step in the synthesis, catalyzed by acetohydroxyacid isomeroreductase, involves shift of an alkyl group (Fig. 24-17). Neither this reaction nor the preceding one occurs in mammals. For this reason, the enzymes required are both attractive targets for herbicide design.343 346 The third enzyme, dihydroxy acid dehydratase, catalyzes dehydration followed by tautomerization, resembling 6-phospho-... 

Several instances ore known in which a unsaturated acids yield ./ -dihydroxy acids on treatment with peracetic aoid and alkaline hydrolysis of the resultant 1,2-diol monoesters. 37- Although... 

Conversion of the acetohydroxy acids to the a,/3-dihydroxyacid precursors of valine and isoleucine is catalyzed by acetohydroxy acid isomeroreductase. The a,/3-dihydroxy acids are both converted to the a-keto acid precursors of valine and isoleucine by a dihydroxy acid dehydrase. Finally, the two amino acids are formed in trans-... 

The dihydroxy acid that is formed in this step cyclizes to the S-lactone mevalonolactone. 

The method (scheme 1) was targeted to the utilization of readily available carbohydrate sources such as lactose, maltose starch and maltodextrins. It was applicable largely to the preparation of the (S)-acid 1 and the lactone 2 since naturally occurring hexoses have almost exclusively the D-configuration and the C5 carbon becomes the chiral center in the dihydroxy acid. More recently, direct access to the (R)-isomers 4 and 5 was made possible by the development of a similar oxidation method using 5-linked pentoses as the starting compounds... 

The acid is also produced when ammonium hydroxide is added in the requisite amount to a solution of the tetrachlor-dihydroxy acid ... 

T etrabr om-dihydr oxy-platinic Acid, HaPtBr4(0H)2. — Platinum tetrabromide is only slightly soluble in water, yielding a reddish brown solution containing the dihydroxy acid. With silver nitrate the acid solution yields a dark brown precipitate of the silver salt,7 Ag2PtBr4(OH)2. 

The subsequent steps in the French and Czech modifications follow the Woodward synthesis in its broad lines, but it should be noted that Velluz already resolves Woodward s XXXV into optical isomers with the help of either brucine or ephedrine (185). In an analogous study, the Czech investigators resolve a hydroxy acid (XXXVIII), obtained by hydrolysis of the Velluz compound (XXXVII) (185), with the help of brucine (187). Also, another dihydroxy acid (XXXIX), obtained from Woodward s lactone acid (XXXVI), has been resolved, again by use of... 

Dihydroxy acids, preparation, 179 Dihydroxy compounds, alkylation in the Williamson reaction, 227 dehydration, 33, 236 dehydrogenation to lactones, 336 esterification, 481 preparation, by bimolecular reduction of ketones, 134 by cleavage of oxides, 172 by hydrolysis of esters, 169 by reduction of dihydric phenols, 138... 

This method has been employed extensively for the conversion of olefins to glycols and olefinic acids to dihydroxy acids. The best general reagent is performic acid. The olefinic compound is stirred at 40° with... 

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