Lactic acid optical activity

Fio. 2 6.2. (a) Mycomycin, a naturally-occurring optioally-aotiv alien (b) one form of lactic acid (optically active). 

A molecule is chiral if it cannot be superimposed on its mirror image (or if it does not possess an alternating axis of symmetry) and would exhibit optical activity, i.e. lead to the rotation of the plane of polarization of polarized light. Lactic acid, which has the structure (2 mirror images) shown exhibits molecular chirality. In this the central carbon atom is said to be chiral but strictly it is the environment which is chiral. 

In view of the ready availabiUty of optically pure lactic acid derivatives this reaction offers an attractive general method for the preparation of optically pure aromatic ester derivatives (41). Stereoselective alkylation (15—60% inversion) of ben2ene with optically active 1,2- 1,3- and 1,5-dihaloalkanes was also reported (42). 

Lactic acid is also the simplest hydroxy acid that is optically active. L (+)-Lactic acid [79-33-4] (1) occurs naturally ia blood and ia many fermentation products (7). The chemically produced lactic acid is a racemic mixture and some fermentations also produce the racemic mixture or an enantiomeric excess of D (—)-lactic acid [10326-41-7] (2) (8). 

Many of the physical properties are not affected by the optical composition, with the important exception of the melting poiat of the crystalline acid, which is estimated to be 52.7—52.8°C for either optically pure isomer, whereas the reported melting poiat of the racemic mixture ranges from 17 to 33°C (6). The boiling poiat of anhydrous lactic acid has been reported by several authors it was primarily obtained duriag fractionation of lactic acid from its self-esterification product, the dimer lactoyUactic acid [26811-96-1]. The difference between the boiling poiats of racemic and optically active isomers of lactic acid is probably very small (6). The uv spectra of lactic acid and dilactide [95-96-5] which is the cycHc anhydride from two lactic acid molecules, as expected show no chromophores at wavelengths above 250 nm, and lactic acid and dilactide have extinction coefficients of 28 and 111 at 215 nm and 225 nm, respectively (9,10). The iafrared spectra of lactic acid and its derivatives have been extensively studied and a summary is available (6). 

In addition to solvent uses, esters of lactic acid can be used to recover pure lactic acid via hydrolysis, which in-tum is used to make optically active dilactide and subsequently polylactic acid used for drag delivery system.5 This method of recovery for certain lactic acid applications is critical in synthesis of medicinal grade polymer because only optically active polymers with low Tg are useful for drug delivery systems. Lactic acid esters themselves can also be directly converted into polymers, (Figure 1), although the commercial route proceeds via ring-opening polymerization of dilactide. 

Enantiomers have identical chemical and physical properties in the absence of an external chiral influence. This means that 2 and 3 have the same melting point, solubility, chromatographic retention time, infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) spectra. However, there is one property in which chiral compounds differ from achiral compounds and in which enantiomers differ from each other. This property is the direction in which they rotate plane-polarized light, and this is called optical activity or optical rotation. Optical rotation can be interpreted as the outcome of interaction between an enantiomeric compound and polarized light. Thus, enantiomer 3, which rotates plane-polarized light in a clockwise direction, is described as (+)-lactic acid, while enantiomer 2, which has an equal and opposite rotation under the same conditions, is described as (—)-lactic acid. 

In general, the maximum number of optically active isomers is given by 2n where n represents the number of asymmetric carbon atoms. Thus for a compound where n = 1, as in lactic acid, there would be two stereoisomers, one the dextro and the other the laevo. For a compound with two asymmetric carbon atoms, there would be 22 = 4 stereoisomers. But if the two asymmetric carbon atoms carry exactly identical groups, as in tartaric acid, the number would be fewer than four and we know that it exists in three forms, the d the 1 and the meso. 

Acids of established configurations have been used to correlate the configurations of other oxygen-containing optically active compounds. Thus on the basis of lactic acid, the configuration of the simplest optically active alcohol, 2 butanol has been assigned as follows—... 

But if it is esterified with some optically active alcohol (ROH ) and then reduced, the resulting ester on hydrolysis yields an optically active lactic acid. 

Enantiomers have very similar chemical properties, but they rotate polarized light in opposite directions (optical activity, see pp. 36,58). The same applies to the enantiomers of lactic acid. The dextrorotatory L-lactic acid occurs in animal muscle and blood, while the D form produced by microorganisms is found in milk products, for example (see p.l48). The Fischer projection is often used to represent the formulas for chiral centers (cf.p. 58). 

The ring-opening polymerization of dilactide (dimeric cyclic ester of lactic acid) allows the preparation of high molecular weight, optically active polyesters of lactic acid. The configuration of the asymmetric carbon atoms of the monomer is retained when the polymerization is initiated with SnCl4 or Et2Zn, for example ... 

Lactic acid was one of the first biological substances to he investigated from the standpoint of the existence of the two optically active Terms. 

OPTICAL ISOMER- Either of two kinds of optically active three-dimensional isomers (stereoisomers). One kind is represented by mirror-image presence of one or more asymmetric carbon atoms in the compound (glyceraldehyde, lactic acid, sugars, tartaric add, amino acids). The other kind is exemplified by diastereoisomers, which are not mirror images. These occur in compounds having two or more asymmetric carbon atoms thus, such compounds have 2 optical isomers, where n is the number of asymmetric carbon atoms. 

Irvine s first publication (1899) dealt with the rotatory powers of the optically active methoxy- and ethoxy-propionic acids prepared from lactic acid. In those early days the Purdie reaction afforded so rich a field for investigation that Irvine and his collaborators continued work on various types of hydroxy bodies in addition to the sugars. There appeared papers on the isopropylidene derivatives and methyl ethers of glycerol and mannitol, and on the chemistry of benzoin and benzoin-like materials. The constitution of the glucoside salicin was studied and its pentamethyl ether was synthesized. 

In general, small specific rotations should be expected for such adamantane derivatives since a large reduction in optical rotatory power should occur when pairwise interactions are greatly reduced by distance. The resolution of several tetrasubstituted adamantanes (62-65) has been attempted 178 179> 247f Mes-ured rotations, as expected 4> are quite low. Only 65, the formal analogue of lactic acid, has been proven to be optically active 178>179f by a confirmatory approach. 

What is interesting, however, is some of the chemistry that is not present. For example, the petrochemical industry does not have a basic feedstock in the five-carbon area and thus we see few products derived from or based on five-carbon chemistry. Optical active compounds are also missing from the petrochemical-derived product list. For example, lactic acid is now made exclusively from glucose, with the reason being that the fermentation route provides stereochemical purity that is difficult to achieve from petrochemical building blocks. 

The two isomers of lactic acid are mirror images (following fig). A molecule that exists as two non-superimposable mirror images has optical activity if only one of the mirror images is present. 

To what extent the 2-(a do-poly hydroxy alkyl) benzimidazoles can be used in resolving other optically active acids has not been determined. The benzimidazoles are relatively weak bases and do not form stable salts with weakly ionized acids. Haskins and Hudson15 found that when a solution of racemic lactic acid and 2-(D-gluco-D-gulo-hepto-hexa,hydroxy-hexyl)benzimidazole was concentrated, it was the free base that precipitated rather than one of the expected salts. It seems probable, however, that the method will be found useful in other resolutions, especially of the stronger organic acids. 

Reactions of 3-substituted 2-(lV-phenylaminomethyl)piperazines with a slight excess of ethyl 2-chloroacetate under reflux afforded mixtures of 9-substituted 2-phenylperhydropyrido[l,2-a]pyrazin-3- and -4-ones, which could be separated by column chromatography [72JCS(P2)1374], When 2-[(3-trifluoromethylphenyl)aminomethyl]piperidine was heated with optically active ethyl 2-chloropropionate (87MIP1 91TA231), or lactic acid ethyl ester methanesulphonate (91TA231), the product was a C-9a epimeric mixture of 2-(3-trifluoromethylphenyl)-4-methylperhydropyrido[l,2-fl]-pyrazin-3-ones. The reaction between yV-methyl-2-piperidine-carboxamide and hydroxymaleic anhydride in pyridine resulted in 2,3-dimethyl-3-hydroxyperhydropyrido[l,2-a]pyrazine-l,4-dione (74CB2804). 

But the product from the enzymatic reaction is optically active. The two faces of pyruvic acid s carbonyl group are enantiotopic and, by controlling the addition so that it occurs from one face only, the reaction gives a single enantiomer of lactic acid. 

Consider another actual molecule where this property occurs, i.e. lactic acid, CH3C H(OH)COOH. The asterisked carbon atom has four different groups arranged around it (CH3, H, OH and COOH) and so this molecule must be optically active and have two different isomers. We say the starred carbon atom is asymmetric , i.e. not symmetrical. You can draw out the two forms. It is impossible to say which is the d or l form by simply looking at them they must be tested for their twisting properties with polarized light beams. 

An alternative employs classical resolution using lactic acid as the source of asymmetry. Amide formation from (S)-O-acetyllactic acid and 13 gave a separable mixture of 14 [14, 15]. The lactanilides could be eliminated or reduced [16] to remove the stereogenic centre to give optically active analogues of 9 and 11. Nonetheless, a serious problem with the effective use of anilides as auxiliaries is their recovery in enantiomerically pure form. 

When optical rotation data arc expressed in this standard way, the specific rotation, lain, is a physical constant characteristic oTa given opticall> active compound- For example, the (e > lactic acid Uiat we saw in Section 9.1 has al > +3.82 , and (—> Iactic acid has loin -S-Blf - Some additional examples are listed in Table 9 l. 

Arylation of a-Keto Esters. Zirconium complex (1) has been used as a catalyst for the synthesis of optically active 2-(2-hydroxyaiyl)lactic acid ethyl ester (7) (eq 1). ... 

---