Unsaturated from hydroxy acids

Enantiopure amide derivatives (64) of -unsaturated a-hydroxy acids have been made by addition of a vinylsilane, R2R1C=(4ISiMe3, to /V-phcnylglyoxamide.181 The reaction is catalysed by scandium(III) triflate complexed to a C2-symmetric PYBOX ligand derived from (f )-norephedrine. 

The loss of water from hydroxy acids and the formation of unsaturated acids has been met with before in connection with heta-hydroxy mono-basic acids e.g., hydraciylic acid, jS-hydroxy propionic acid, and its conversion into acrylic acid, propenoic acid (p. 172). In such cases the beta-hydioxy acid loses water from two neighboring carbon groups thereby creating a double bond. 

MJnsaturated acids are rarely formed from -hydroxy acids by means of dehydrating agents, which, instead, afford lactides and anhydrides or, with loss of formic acid, aldehydes. However,, / -unsaturated nitriles can be obtained from a-hydroxy nitriles (cyanohydrins) by means of thionyl chloride45 or phosphorus(v) oxide,46 and are readily hydrolysed to the corresponding <%,/ -unsaturated acids. 

Lactones are easily made from hydroxy acids and from unsaturated acids. As expected, the lactones with five- (y-lactone) and six- (8-lactone) raembered rings are... 

P-Hydroxy acids lose water, especially in the presence of an acid catalyst, to give a,P-unsaturated acids, and frequendy P,y-unsaturated acids. P-Hydroxy acids do not form lactones readily because of the difficulty of four-membered ring formation. The simplest P-lactone, P-propiolactone, can be made from ketene and formaldehyde in the presence of methyl borate but not from P-hydroxypropionic acid. P-Propiolactone [57-57-8] is a usehil intermediate for organic synthesis but caution should be exercised when handling this lactone because it is a known carcinogen. 

Interest in synthetic naphthenic acid has grown as the supply of natural product has fluctuated. Oxidation of naphthene-based hydrocarbons has been studied extensively (35—37), but no commercially viable processes are known. Extensive purification schemes must be employed to maximize naphthene content in the feedstock and remove hydroxy acids and nonacidic by-products from the oxidation product. Free-radical addition of carboxylic acids to olefins (38,39) and addition of unsaturated fatty acids to cycloparaffins (40) have also been studied but have not been commercialized. 

Hydroxy radical and sulfate radical anion, though they may sometimes give rise to similar products, show quite different selectivity in their reactions with unsaturated substrates. In particular, the sulfate radical anion has a somewhat lower propensity for hydrogen abstraction than the hydroxyl radical. For example, the sulfate radical anion shows little tendency to abstract hydrogen from mcthacrylic acid.232... 

A number of amide- and ester-linked fatty acids and (/ )-3-hydroxy acids are components of the lipid A part in the LPS from Gram-negative bacteria. The acids have been tabulatedand the chemistry of lipid A summarized. The most common acids in lipid A from Enterobacteriaceae are the saturated 12 0,14 0, and 16 0, and the (/ )-3-hydroxy-14 0, The last is linked to N-2 and 0-3 of the 2-amino-2-deoxy-D-glucopyranosyl residues, and the others are ester-linked to the hydroxy acid, as in the lipid A (44) of Salmonella minnesota. Other linear and branched fatty acids, unsaturated acids, S)-2- and (/ )-3-hydroxy acids, and 3-oxotetradecanoic acid are components of lipid A from certain different species. In the lipid A from Rhizobium trifolii, 2,7-dihydroxyoctanoic acid is linked as amide to a 2-amino-2-deoxy-D-gl ucopy ranosy 1 residue. ... 

It will be seen that the enediolic system can theoretically be written in the isomeric 2-keto (II) or 3-keto (III) forms and these in turn are seen to be derived from the 2-keto and the 3-keto acids IV and V, respectively (compare with benzoin which reacts with iodine in an analogous fashion to L-ascorbic acid). Consequently the synthesis of L-ascorbic acid and of its analogs has consisted in devising methods for the formation of 2-keto or 3-keto hydroxy acids followed by their enolization and lactonization. Four main methods are available for the synthesis of analogs of L-ascorbic acid containing the characteristic five-membered unsaturated enediolic ring. 

The photoelectrochemical synthesis of amino acids from simple molecules has also been reported. Low efficiencies were observed in the conversion of mixtures of methane, ammonia and water to several amino acids on platinized TiOz Amino acids and peptides were reported when glucose replaced methane as the carbon source in a parallel experiment Higher quantum efficiencies (20-40%) were observed in the conversion of alpha-keto acids or alpha-hydroxy acids to the corresponding alpha-amino acids Moderate levels of enantiomeric selectivity (optical yields of about 50%) were reported when chiral starting materials were employed. Photoinduced Michael-like reactions were observed when alpha, beta unsaturated acids were used as substrates for the amino acid synthesis... 

Asymmetric bromolactonization (8, 421-423). Full details for synthesis of a,a-disubstituted a-hydroxy acids from a,/S-unsaturated acids by bromolactonization have been published.1... 

The fatty acids consist of a mixture of normal and a-hydroxy acids, in the ratio of 3 1, that include a broad range of acids differing in their chain length (from 13 to 25 carbon atoms). The normal acids are mainly saturated the major component is the C15 acid (32.5%). Among the a-hydroxy acids, 30% of the mixture is made up of unsaturated acids the major components are C24 0, C22 0, and C22 1 a-hydroxy acids.141... 

The reported number of lanolin acids (C7 to C41) varies dramatically from 32 to 138.17 18 21,23-26 The possible explanation for this discrepancy is that different methods were used to produce the alcohols.8 The lanolin acids comprise four major classes normal, iso (co-l-methyl substituted), anteiso (co-2-methyl substituted), and a- and co-hydroxy acids. The relative proportions are 12.1% normal acids, 22.1% iso acids, 26.3% anteiso, 27.1% a-hydroxy acids, and 5.1% co-hydroxy acids.27 28 Minor constituents include polyhydroxy acids (4.7%) and unsaturated acids (2.1%).23-25... 

Hydroxydec-2-enoic acid 397 was identified in the fodder juice of the Weisel cells (gelee royale) of honey bees. One of the synthesis of 397 starts from suberic acid ethylester 393 222) which was first converted into the hydroxyacid 394 and then into the thiol ester 395. Raney nickel reduction of the latter yields an intermediate aldehyde which, in statu nascendi, reacts with the phosphorane 67 to give 396. Subsequent hydrolysis of396affords the ( )-a,0-unsaturated hydroxy acid 397 222) (Scheme 70). 

Asymmetric Halolactonization. An asymmetric halolac-tonization reaction using proline as a chiral auxiliary has been reported. Optically active a-hydroxy acids (16) are prepared from a,p-unsaturated acids via the corresponding (S)-proline amide (13) involving an asymmetric bromolactonization step (eq 6) ... 

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