D-Lactic Acid Derivatives

The purpose of this section is not to reiterate the chemistry of L- lactic acid and apply it to the corresponding D-lactic acid, but rather to focus on the uses of D-lactic acid derivatives for the syntheses of potentially useful chemical intermediates, biologically active compounds, and natural products. 

Fortunately, a host of methods is available for achieving this goal. They include resolution of a D,L-mixture [238] inversion of L-lactic acid derivatives (see Sections 1.2.1.2 and 1.2.2.2) asymmetric reduction of pyruvates catalytically [239], enzymatically [240], or with chiral boranes [241] and diazotization of D-alanine derivatives, which proceeds with net retention of configuration [242,243]. In addition, D-lactic acid can be obtained by the fermentation of glucose with Lactobacillus leichmannii in the presence of calcium carbonate [244], 

The hetero Diels-Alder reaction (909 — 910) produces a 5 1 mixture of diastereomers from which cis-910 is isolated by flash chromatography (95% optically pure). Reduction of the ketone carbonyl followed by methanolysis furnishes the axial glycoside 911. The furan heterocycle behaves as a masked carboxylic acid function that can be liberated by oxidation with ruthenium tetraoxide. The conversion of 911 to 912 requires 13 steps. 

Allylboronate 940, a chiral allylic alcohol a-carbanion equivalent, reacts with aldehyde 929 as a matched pair giving adduct 941 as an 89 11 mixture of diastereomers. A similar 

Epoxidation of the olefin occurs with high diastereofacial selectivity to give carbamoyl-oxirane 945. This epoxide is not extremely stable, and is treated directly with methanesulfonic acid to afford the j5-D- a/o-furanoside 946. The stereocenter at C-2 must be inverted to match the configuration of the natural product. This is accomplished by triflate formation followed by an Sn2 reaction with cesium acetate. Hydrolysis of the OAc group furnishes the desired P D-ga/ac o-furanoside (947). 0-Methylation, benzyl group hydrogenolysis, acidic hydrolysis, and dithioacetal formation completes the synthesis of 948 in 11 steps and 5.7% overall yield from 929 [252]. 

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Gorton et al. reported carbon paste electrodes based on Toluidine Blue O (TBO)-methacrylate co-polymers or ethylenediamine polymer derivative and NAD" " with yeast alcohol dehydrogenase for the analysis of ethanol [152,153] and with D-lactate dehydrogenase for the analysis of D-lactic acid [154]. Use of electrodes prepared with dye-modified polymeric electron transfer systems and NAD+/NADH to detect vitamin K and pyruvic acid has also been reported by Okamoto et al. [153]. Although these sensors showed acceptable performances, insensitivity to ambient oxygen concentration, sensor stability and lifetime still need to be improved to obtain optimal dehydrogenase based enzyme biosensors. 

PLA An important feature of the lactic acid is its ability to exist in two optically active forms l- and D-isomers. Lactic acid derived from fermentation consists of 99.5% L-isomer and 0.5% o-isomer. The production of the cyclic lactide dimer intermediates results in three potential l-, d-, and l/d (wso)-forms and a racemic equal mixture of d- and L-forms. The l- and o-forms are optically active while the meso-foxm and the racemic mixture are optically inactive (Fig. 2). 

Table 2. The family of glycolic and lactic acid-derived aliphatic polyesters (X and Y stands for the percentage of L-acid and glycolic acid units in the polymer chain, respectively, the content in D-units bdiig given by die conqilemoit to 100%)...

Over the past several decades, polylactide - i.e. poly(lactic acid) (PLA) - and its copolymers have attracted significant attention in environmental, biomedical, and pharmaceutical applications as well as alternatives to petro-based polymers [1-18], Plant-derived carbohydrates such as glucose, which is derived from corn, are most frequently used as raw materials of PLA. Among their applications as alternatives to petro-based polymers, packaging applications are the primary ones. Poly(lactic acid)s can be synthesized either by direct polycondensation of lactic acid (lUPAC name 2-hydroxypropanoic acid) or by ring-opening polymerization (ROP) of lactide (LA) (lUPAC name 3,6-dimethyl-l,4-dioxane-2,5-dione). Lactic acid is optically active and has two enantiomeric forms, that is, L- and D- (S- and R-). Lactide is a cyclic dimer of lactic acid that has three possible stereoisomers (i) L-lactide (LLA), which is composed of two L-lactic acids, (ii) D-lactide (DLA), which is composed of two D-lactic acids, and (iii) meso-lactide (MLA), which is composed of an L-lactic acid and a D-lactic acid. Due to the two enantiomeric forms of lactic acids, their homopolymers are stereoisomeric and their crystallizability, physical properties, and processability depend on their tacticity, optical purity, and molecular weight the latter two are dominant factors. 

Lactic acid is produced by the fermentation of carbohydrate material, usually glucose derived by hydrolysis from starch. The fermentation route can provide either enantiomer of lactic acid in high purity and dominates over chemical routes. The structure of lactic acid contains one asymmetric carbon, and can therefore exist as two stereoisomers. L-lactic acid is present naturally in numerous organisms, whilst the mirror image D-lactic acid is very rare in nature. 

Kefir is also prepared from commercial starters using bovine milk and it has been reported that the lactose concentration effectively decreased from 4.92%(w/v) to 4.02%(w/v) and the L(+)- lactic acid concentration increased to 0.76%(w/v) from 0.01%(w/v) after 24 hours of incubation. The acetic acid content increased from 2.10 to 2.73 mg/ml while the pH value was reported to be low as 4.24 in the first 24 hours after which it decreased gradually. The concentration of L(+)- lactic acid subsequently decreased while that of D(-)- lactic acid subsequently increased. These fermentation values depend on the type of starter culture used, the storage period and the medium used to grow the kefir (for example the mammalian species from which the milk is derived, the coconut water, etc.), (Garcia Fontan, Martinez, Franco, Carballo, 2006 Magalhaes, Pereira, et al., 2011 Oner, Karahan, 0akmak9i, 2010). 

Lactic acid is another secondary product of fermentation. It is also derived from pyruvic acid, directly reduced by yeast L(+) and d(—) lacticodehydrogenases. In anaerobiosis (the case in alcoholic fermentation), the yeast synthesizes predominantly d(—) lacticodehydrogenase. Yeasts form 200-300 mg of D(-) lactic acid per liter and only about a dozen milligrams of L(+) lactic acid. The latter is formed essentially at the start of fermentation. By determining the D(—) lactic acid concentration in a wine, it can be ascertained whether the origin of acetic acid is yeast or lactic bacteria (Section 14.2.3). Wines that have undergone malolactic fermentation can contain several grams per liter of exclusively L(- -) lactic acid. On... 

Bartlett, P. A., D. J. Tanzella, and J. F. Barstow Ester-enolate Claisen rearrangement of lactic acid derivatives. J. Organ. Chem. (USA) 47, 3941 (1982). 

Racemic dinitropyridyl, dinitrophenyl, and dinitrobenzoyl amino acids were resolved on C-18W/UV TLC and HPTLC plates (Macherey-Nagel) developed with 2% aqueous isopropanol containing 2-5% BSA. Development times were 1-2 h, and visualization was under 254 nm UV hght. Ri differences ranged from 0.06 to 0.49 [34]. The same plates with mobile phases composed of isopropanol -E BSA-E sodium tetraborate, acetic acid, or sodium carbonate served to separate enantiomeric D,L-methylthiohydantoin andphenylthiohydantoin derivatives of amino acids, kynureyne, 3-(l-naphthyl)alanine, lactic acid derivatives, alanine and leucine p-nitroanilides, and 2,2,2-trifluoro-l-(9-anthryl)ethanol [35], and with mobile phases composed of water with 5-7% BSA -E 2% isopropanol to separate dansyl amino acid derivatives [36]. 

Listowsky and coworkers showed that the c.d. of this sugar derivative is due entirely to lactic acid, and confirmed that this chromophore is in the D configuration for muramic acid. N-Acetylmuramic acid, in which the amino group is replaced by an amido group at C-2, has a c.d. spectrum that is roughly a linear combination of the lactic acid in muramic acid and the amide in 2-acetamido-2-deoxy-D-glucose. This indicates that the amide chromophore and the lactic acid chromophore in N-acetylmuramic acid behave independently. 

Fig. 3 Examples of monomer units having reactive side-chain groups, which can be copolymerized with polyesters (a) a-malic acid, (b) [S-malic acid, (c) a-carboxyl- -caprolactone, (d) carboxy lactic acid, (e) trimethylene carbonate derivative, and (1) depsipeptide...

The above observations suggested that hexoses arise in Nature by reaction of glycerose with dihydroxyacetone. A vast amount of practical information has been derived from investigation of plant- and muscle-extracts, two dissimilar systems that show many similarities in their biosynthetic manipulations. There is a close parallelism in the sequence of intermediates involved in the processes wherein D-glucose is converted to ethanol and carbon dioxide by yeasts, and to lactic acid by muscle during contraction. The importance of these schemes lies in their reversibility, which provides a means of biosynthesis from small molecules. 

In the above cited example [/ (a)] the rotation of the plane of polarization is to the right (clockwise), the lactic acid is dextrorotatory (Latin dexter = right) designated by d if the rotation is to the left (counterclockwise), the lactic acid [/ (h) is levorotatoiy (Latin laevus = left) designated by 7 . In the same vein, the example [ii (h) represents 1-2 methyl-1-butanol a product derived from fusel oil. 

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