2- -1,2-hydroxypropanoic acid, synthesis

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. 

Abdel-Rahman, H.M. and Hussein, M.A. 2006. Synthesis of P-hydroxypropanoic acid derivatives as potential antiinflammatory, analgesic and antimicrobial agents. Archives in Pharmacology, 339 378-87. 

The enantiotopic discrimination of hydrogens during oxidatitm of unactivated C—bonds by microorganisms is synthetically extremely useful, and some examples are shown in Scheme The resultant products are valuable chiral synthons. For example (/ )-3-hydroxybutanoic acid (7) a versatile homochiral synthon, can be used in e synthesis of antibacterials. (5)-2-Methyl-3-hydroxypropanoic acid (8) has been widely employed as a source of chirality, for example in the synthesis of maysine, macrolide antibiotics and both (i )- and (S)-muscone. A variety of other optically active 3-hydroxy aliphatic carboxylic acids can be prepared by analogous methods. 

Both enantiomers of lactic acid (2-hydroxypropanoic acid) are natural products and easily obtained by biotechnological methods, so there is no need for their synthesis in the laboratory. Even their esters with alkanols, e.g.. 1, are comparatively inexpensive and, therefore, convenient starting materials for derivatization to chiral reagents and auxiliaries. If necessary, such esters can be obtained by any convenient esterification technique. O-Acylated derivatives of lactic esters have been used very successfully as chiral auxiliaries in diastereoselective Diels-Alder reactions (Section D.1.6.1.1.1.1.2.). The acrylate 2 and methacrylate 31-3 and the fu-marate 43 give very high enantiomeric excesses. These are obtained from the lactic ester by treatment with an acid chloride. 

Synthesis of (S)- and (/ )-3-aryl-3-hydroxypropanoic acids using different carbonyl reductases (CR1, carbonyl reductase from Candida magnoliae CR2, alcohol dehydrogenase from Saccharomyces cerevisiae) and different nitrilases (nitrilase 1 from Synechocystis sp., nitrilase 2 from BradyrhizobiumJaponicum) [58],... 

Compound (VIII.98), a folic acid analogue with a y-fluoro substituent in the side-chain was described first by Alekseeva e/ al. [281] and several years later by Bergmann and Chun-Hsu [282]. The synthesis of (VIII.98), as mixture of threo and erythro isomers, was achieved via the Waller method from V-(4-ami-nobenzoyl)-y-fluoroglutamic acid, 2,4,5-triamino-6(lif)-pyrimidinone, and 2,3-dibromopropionaldehyde, but the yield was low (5.6%). y-Fluoroglutamic acid, as a mixture of D- and L-enantiomers, was prepared from diethyl 2-fluoromalonate by condensation with ethyl 2-acetamidoacrylate followed by hydrolysis and decarboxylation in refluxing 12 M HCl, or from ethyl 3-chloro-2-hydroxypropanoate by a sequence consisting of (i) 0-t-butylation with CH2 = C(CH3)2, (ii) condensation with diethyl 2-acetamidomalonate, (hi)... 

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