3-hydroxycarboxylic acids

The carbonylation of alkene in AcOH-acetic anhydride in the presence of NaCl affords the /9-acetoxycarboxylic anhydride 242 in good yields and the method offers a good synthetic method for / -hydroxycarboxylic acid 243[222],... 

ALKANOLAMINES - ALKANOLAMINESFROMNITROALCOHOLS] (Vol2) -esters of lactate salts [HYDROXYCARBOXYLIC ACIDS] (Vol 13)... 

Lactic acid [50-21-5] (2-hydroxypropanoic acid), CH CHOHCOOH, is the most widely occurring hydroxycarboxylic acid and thus is the principal topic of this article. It was first discovered ia 1780 by the Swedish chemist Scheele. Lactic acid is a naturally occurring organic acid that can be produced by fermentation or chemical synthesis. It is present ia many foods both naturally or as a product of in situ microbial fermentation, as ia sauerkraut, yogurt, buttermilk, sourdough breads, and many other fermented foods. Lactic acid is also a principal metaboHc iatermediate ia most living organisms, from anaerobic prokaryotes to humans. 

Other multifunctional hydroxycarboxylic acids are mevalonic and aldonic acids which can be prepared for specialized uses as aldol reaction products (mevalonic acid [150-97-0] (13)) and mild oxidation of aldoses (aldonic acids). 

Many natural and synthetic organic compounds are hydroxy dicarboxyhc acids (see also Hydroxycarboxylic acids). This article discusses mainly malic and tartaric acids thiomalic acid is included because of its stmctural similarity to malic acid. 

OC-Hydroxycarboxylic Acid Complexes. Water-soluble titanium lactate complexes can be prepared by reactions of an aqueous solution of a titanium salt, such as TiCl, titanyl sulfate, or titanyl nitrate, with calcium, strontium, or barium lactate. The insoluble metal sulfate is filtered off and the filtrate neutralized using an alkaline metal hydroxide or carbonate, ammonium hydroxide, amine, or alkanolamine (78,79). Similar solutions of titanium lactate, malate, tartrate, and citrate can be produced by hydrolyzation of titanium salts, such as TiCl, in strongly (>pH 10) alkaline water isolation of the... 

An example of an exo-trig process would be lactonization of a m-hydroxycarboxylic acid ... 

When applied to 5- or 6-hydroxycarboxylic acids, this reaction gives cycliza tion products m good yield [99] (equations 50 and 51)... 

Oxy-aldehyd, n, hydroxy aldehyde, -ammo-niak, n, oxyammonia (hydroxylamine), -azoverbindung, /. hydroxyazo compound, -benzol, n, hydroxybenzene (phenol), -bem-steinsaure. /, hydroxysuccinic acid (malic acid). -biazol, n. oxadiazole, oxdiazole. -bitumen, n, oxidized bitumen, -carbon-s ure, /, hydroxycarboxylic acid, -chlnoltn, n. hydroxyquinoline, -clunon, n. hydroxy-quinone. -chlorid, n. oxychloride, -chlor-kupfer, n. copper oxychloride, -cyan, n. oxycyanogen. 

These chelatoborates are synthesized by reactions of aromatic diols (e.g., pyrocate-chol), hydroxycarboxylic acids (e.g., salicylic acid), or other aromatic OH-... 

Once again, desilylation and oxidative cleavage33 delivers the hydroxycarboxylic acids. A chairlike transition state model, analogous to that proposed for the corresponding boron enolate33, is postulated in order to rationalize the ul topicity of the above titanium enolate. 

Boron enolates containing the chiral information in C2-symmetric ligands of the metal atom, also provide rmt/-/ -hydroxycarboxylic acid derivatives of high optical purity34 -64-70. When 5-(3-cthylpent-3-yl) thiopropanoate is treated with (5,5)-2,5-dimethyl-l-(trifluoromethylsul-... 

Alkaline hydrolysis of the adducts 6 and 7, which is fairly mild in the case of the imide adducts, liberates 3-hydroxycarboxylic acids 8 or ent-8 and simultaneously regenerates the chiral auxiliary reagent. Furthermore, both enantiomers of the 3-hydroxycarboxylic acid are available in almost optically pure form depending on which reagent is chosen as the starting material. 

Table 1. svn-3-Hydroxycarboxylic Acids From Cyclic A-(t-Ox-opropyllamides or -imides via Metal Hitolates by Addition of... 

Similar methodology has been applied in the syntheses of 2-amino-3-hydroxycarboxylic acids in high diastereomeric and enantiomeric purity. Two separate pathways give either the antt- or. WM-products. The first strategy relies on haloacetate precursors derived either from (S )-valine 17"- oi or from norephedrine 18102, which are converted into the boron enolates103 and subsequently reacted with aldehydes to deliver. ym-adducts99 102. The diastereomeric ratio, defined as the ratio of the desired diastereomer/the sum of all others, is 50 1 for the former and about 95 5 for the latter adducts. 

When the latter adduct (R = CFI3), purified by chromatography, is treated with sodium azide (inversion of configuration) and subsequently subjected to alkaline hydrolysis and hydrogenation, the enantiomerically pure 2-amino-3-hydroxycarboxylic acid results102 ... 

The second approach for the synthesis of 2-amino-3-hydroxycarboxylic acids starts with a chiral isothiocyanate which is added, via the tin enolate, to aldehydes. The initially formed adducts are immediately derivatized to the heterocycles, from which. yj 7-2-amino-3-hy-droxycarboxylic acids result after a three-step procedure. The diastereomeric ratios of the intermediate bis-heterocyclic products range from 93 7 to 99 1 (desired isomer/sum of all others)104. 

An entry to. yyrt-2-methoxy-3-hydroxycarboxylic acids is also opened using similar methodology. Thus the norephedrine derived (4/ ,5S)-3-(2-methoxy-l-oxoethyl)-4-methyl-5-phenyl-1,3-oxazolidine-2-one 23105a, as well as the phenylalanine derived (4S)-4-benzyl-3-(2-methoxy-l-oxoethyl)-l,3-oxazolidin-2-one 25105b, can be added to aldehydes via the boron enolates to give, after oxidative workup, the adducts in a stereoselective manner (d.r. 96 4, main product/sum of all others). Subsequent methanolysis affords the methyl esters. 

A way to anh-configurated a-amino-/ -hydroxycarboxylic acids is opened by the aldol addition of oxazolidine amides 7a and 7b. The method1061 is illustrated by a synthesis of (2R,3R)-p-hydroxyleucine (9) which is available from the major diastereomeric adduct 8 (d.r. 92 8) upon successive treatment with 1 N HC1 (30 min). 5 N HCl (100 C, 12 h), and propylene oxide (reflux in ethanol, 30 min). 

Acetylsultam 15 is also used for stereoselective syntheses of a-unsubstituted /1-hydroxy-carboxylic acids. Thus, conversion of 15 into the silyl-A/O-ketene acetal 16 and subsequent titanium(IV) chloride mediated addition to aldehydes lead to the predominant formation of the diastereomers 17. After separation of the minor diastereomer by flash chromatography, alkaline hydrolysis delivers /f-hydroxycarboxylic acids 18, with liberation of the chiral auxiliary reagent 1919. 

In Refomiatsky reactions of + )-trans-(2-phenyleyclohex-l-yl)bromoacetaie with benz-aldehydc, acetophenone. 1-naphthaldehyde and butanal, the corresponding /1-hydroxycarboxylic acids arc obtained, after saponification, in 11-89% ee ... 

Loss of C(0)0CH3 from methyl esters Loss of OC3H7 from propyl esters Methyl esters of 2-hydroxycarboxylic acids Loss of CH3C(0)0 from sugar acetates... 

Methyl esters of unsaturated acids (loss of CH3OH + HzO) Methyl esters of straight-chain hydroxycarboxylic acids except 2-hydroxy acids... 

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