Lactic acid Inactive

A number of functional sialyl Lewis mimetics have been synthesized. Their activities in vitro are equal or even better than those of the tetrasac-charide itself. To overcome synthetic problems, efficient stereoselective glycosylations as well as new chemoenzymatic methods for C-C bond formations had to be developed. The substitution of neuraminic acid by (5)-phenyl- and (5)-cyclohexyl lactic acid, as less flexible glycol acid residues, turned out to be very successful [10]. Also, a phosphate and a sulfate group, respectively, mimic neuraminic acid without loss of activity [11]. (5)-Cyclohexyl lactic acid-mimetic 2 shows a more than ten-fold efficacy compared with sialyl Lewis, whereas the corresponding (/ )-isomer 3 is almost inactive [10]. The deviating orientation of the carboxylic acid functionality compared to the bioactive sialyl Lewis conformation leads to the examined loss of activity. It was shown by transfer-NOE measurements of the corresponding E-selectin complexes that the coordinates of the bioactive conformation of sialyl Lewis and of compound 2 are similar. Con.se-quently structure 2 should bind to E-selectin in the same manner as that of sialyl Lewis [ 10a, b]. 

Disposition in the Body. Readily absorbed after oral administration and widely distributed throughout the tissues. It is rapidly metabolised to the inactive metabolites, j5-(o-tolyloxy)lactic acid and )S-(2-methyl-4-hydroxyphenoxy)lactic acid. Less than 2% of a dose is excreted in the urine as unchanged drug. 

The importance of this covalent control is illustrated in people with a phosphatase deficiency. Because pyruvate dehydrogenase is always phosphorylated and thus inactive, glucose is processed to lactic acid. This condition results in unremitting lactic acidosis (high Wood levels of lactic acid), which leads to the malfunctioning of many tissues, most notably the central nervous system (Section 17.3.2). 

The first really definitive work on glutose was carried out by Benedict, Dakin and West. They showed that glutose in vitro resembles D-fructose in that it is converted by sodium hydroxide into hydroxy acids (principally optically inactive lactic acid) to about the same extent as D-glucose. In slightly alkaline solution phenylhydrazine reacts to form the phenylosazone of methylglyoxal, and zinc ammonium hydroxide converts glutose into methylimidazole in yield comparable to that obtained from fermentable hexoses. But in vivo glutose ... 

Levo Lactic Acid.— Levo lactic acid was first obtained by the fermentation of cane sugar by specific bacteria. It is levo rotatory but, like the dextro acid, the rotation of its salts and its anhydride is reversed, being dextro rotatory. The levo lactic acid and also the dextro acid may be obtained by splitting the inactive acid into its optical components by means of its strychnine salt. 

Stereo Isomerism of Malic Acid.—On examination of the formula of malic acid it will be seen that one of the carbons is asymmetric i.e.j it has united to it four different elements or groups, viz., (—H), (—OH), (—COOH), and (—CH2—COOH). We should, therefore, expect to find that malic acid is optically active and that it exists in the three forms of dextroj levo, and inactive. This is in accordance with the facts. The formulas for the three stereo-isomeric forms of malic acid may be written as follows, corresponding exactly to those for lactic acid. 

One of the above formulas may be taken to represent the dextro form and the other the levo. The mixture of the two will produce the inactive acid. Now these three forms of tartaric acid are all known and they bear to each other exactly the same relation as has been explained in connection with lactic acid. The inactive form is able to be split into its two optical components like the inactive lactic acid. These three acids are as follows,... 

It is this fourth unresolvable inactive tartaric acid which gives to tartaric acid its especial interest and importance in connection with the theory of stereo-isomerism. This acid, like the other three, has been fully explained in accordance with the tetra-hedral theory of van t Hoff and LeBel. The explanation rests upon the fact that there is a second asymmetric carbon atom in tartaric acid. We may construct, by models, or, by drawings, space-formulas for tartaric acid. According to the tetra-hedral theory, the dextro, levo and racemic inactive forms will be as follows, analogous to the corresponding formulas for the three lactic acids. The meso-tartaric acid is represented by the third drawing. 

SLe mimics 46 to 48, which had the GlcNAc unit replaced by (R,/ )-cyclohexan-l,2-diol and sialic acid substituted by glycolic acid or (5)-cyclohexyl lactic acid, were active as antagonists (Figure 16.21). These observations are in agreement with predictions based on computational studies that suggested these compounds are able to adopt the bioactive conformation. These computational simulations further predicted that the (/f)-lactic acid isomers were inactive because of their inability to properly orient the pharmacophores. Indeed, replacement of sialic acid by... 

If, on the other hand, we replace this hydroxyl by H, we form succinic acid, which, like the ethylene lactic acid, is inactive. 

Optical activity was first studied in compounds of carbon. In 1874 van t Hoff showed how optical activity could arise if the four bonds from a carbon atom were arranged tetrahedrally. Le Bel independently, and almost simultaneously, put forward somewhat similar views. A molecule Cubed in which a C atom is attached to four different atoms or groups should exist in two forms related as object and mirror image. The central C atom was described as an asymmetric C atom. A simple molecule of this sort is that of lactic acid, CH(CH3XOH)COOH, which exists in d- and /-forms. There is a third form of such a compound, the racemic form. A true racemate has a characteristic structure different from that of the active forms, there being equal numbers of d- and /-molecules in the unit cell of the crystal, which is optically inactive. We may note that inactive crystalline forms of optically active compounds are not necessarily racemates. For example, the inactive 3-phenylglyceric acid (m.p. 141°C) is not a racemate but the crystals are built of submicroscopic lamellae which are alternately d- and /-rotatory. Slow recrystallization yields single crystals of the d- and /-forms (m.p. 164°C).( ... 

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). 

OnniNAaT Lactio Acid—Lactic acid fermerdaiion—Oj icdUy inactive... 

A mixture of equal amounts of two enantiomers—such as (/ )-(—)-lactic acid and (6 j-(+)-lactic acid—is called a racemic mixture or a racemate. Racemic mixtures do not rotate the plane of polarized light. They are optically inactive because for every molecule in a racemic mixture that rotates the plane of polarization in one direction, there is a mirror-image molecule that rotates the plane in the opposite direction. As a result, the light emerges from a racemic mixture with its plane of polarization unchanged. The symbol ( ) is used to specify a racemic mixture. Thus, ( )-2-bromobutane indicates a mixture of (-l-)-2-bromobutane and an equal amount of (-)-2-bromobutane. 

Ethyleno-lactic acid may be obtained from muscular tissue or from Liebig s extract of meat. It is optically inactive, as are also-solutions of its salts its zinc salt contains 2 Aq, and is very soluble in water and quite soluble in alcohol. When oxidized by chromic acid it yields malonic acid. 

Ordinary liactic Acid—Lactic acid of fermentation—Optically inactive ethylidene lactic acid—Acidum lacticum (tT. S.)—exists in nature, widely distributed in the vegetable kingdom, and as the product of a fermentation which is designated as the lactic, in milk, sour-krout, fermented beet-juice, and rice, and in the liquid refuse of starch factories and tanneries. 

Inactive lactic acid results when lactic acid is prepared by the synthetic methods which have been mentioned (294). The inactive acid may be separated into its constituents by the use of certain general methods which have been found applicable in such cases. While the salts of the dextro and levo forms of active acids with a metallic element have the same solubility, and can not, therefore, be separated by crystallization, the salts formed from these acids and certain organic bases which are optically active differ in solubility. By the fractional crystallization of the strychnine salt of inactive lactic acid, two salts can be separated. The acids obtained from these differ in their action on polarized light one is dextro-rotatory, and the other levo-rotatory. 

An active form of an acid may be obtained from the inactive variety by subjecting it to the action of certain bacteria, which destroy one form of the acid more rapidly than the other. In the case of lactic acid the dextro form may be obtained by the action of the mould called penicillium glaucum on inactive ammonium lactate. When lactic acid is made by the fermenta-... 

The chemical properties of d-lactic acid are identical with those of the inactive acid. Both acids yield the same compounds when they enter into reactions with other substances. The proofs of the structure of z-lactic acid which have been given apply in the case of d-lactic acid. The isomerism is to be attributed, therefore, to the space relations of the atoms. The same statements in regard to structure hold true in the case of Z-lactic acid. 

There is a marked difference between the two inactive forms. Racemic acid may be separated into d- and Z-tartaric acid by the methods which have been described under i-lactic acid. Mesotartaric acid, not being a mixture of different kinds of molecules, can not be so separated. It is changed into the active form of tartaric acid only by the application of heat, when the molecule undergoes decomposition and a new arrangement of atoms is brought about. 

Pasteur s observations began to connect with others. For example, in 1770 Scheele had isolated lactic acid [CHjCH(OH)COOH] from fermented milk. In 1807, Berzelius isolated lactic acid from muscles. Subsequently, lactic acid from fermented milk was found to be optically inactive while that from muscle was found to be optically active. What was the origin of this dichotomy ... 

The solution to the lactic acid dichotomy was now clear. Lactic acid has an asymmetric carbon atom. The four different groups (R to in structures 1 and II or III and IV of Figure 300) are H, CH3, OH, and COOH. Scheele s lactic acid from fermented milk had both enantiomers in equal quantity (the racemate) and was optically inactive, while Berzelius lactic acid from muscle was optically active because only one enantiomer was present. 

Lactic acid played a central role in the development of stereochemistry. It was first isolated by Scheele from fermented milk in 1770. Berzelius isolated lactic acid from muscles in 1807. Following the development of polarimetry in the early nineteenth century, Scheele s lactic acid was found to be optically inactive while Berzelius lactic acid, identical with Scheele s in all other respects, was optically active. Van t Hoff and LeBel both explained these phenomena by postulating that Berzelius lactic acid, derived from muscles, contained only one enan-... 

Anyone who goes from a long period of inactivity to vigorous exercise (for example, from months of watching television to several hours of racquetball) experiences stiffness due to the buildup of lactic acid in the tissues. Even during moderate exercise, muscle activity generates the weak acid carbon dioxide. For example, if glucose is oxidized to water and carbon dioxide and the enzyme carbonic anhydrase interconverts CO2 and carbonic acid ... 

A mixture of the (+) and (-) enantiomers in equal proportions is called a racemic modification (racemate) and is optically inactive. The optical inactivity results from the rotation caused by one enantiomer canceling out that produced by its complementary enantiomer. The racemic modification is designated as ( ) e.g. ( ) lactic acid). As the enantiomers of a substance have identical physical properties, they cannot be easily resolved employing the usual separation techniques such as fractional distillation. As a result, the isolation of optical isomers often pose difficult separation problems and it is usually necessary to resort to some very special techniques to achieve a satisfactory resolution hence the raison d etre for this book. 

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