L-Lactic acid derivatives

Acetylenic diols, potential building blocks for the synthesis of L-hexoses and L-pentoses, are available with either syn or anti configuration using TBPS-protected L-lactic acid derivatives as the chiral source (Scheme 108). 

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],... 

By enantiotopos-differentiating deprotonation the lithiated complex is formed in a reagent-controlled reaction with excellent selectivity. The lithiated center of the complex is assumed to have the S configuration, as follows from the carboxylation, to give an (7 )-lactic acid derivative based on the reasonable assumption of metalloretentive electrophilic attack. Trapping with chlorotrimethylstannane gave the corresponding chiral (.S -SjS-dimethyl-l-trimethylstannyl-alkyl-l-oxa-4-azaspiro[4.5]decane-4-carboxylates. Enantioselectivity of the overall transformation is excellent. 

Both (— )-hyoscine and (— )-hyoscyamine are esters of levorotatory tropic acid, which represents the asymmetric moiety of these alkaloids. Freudenberg et al. 32) found that a series of derivatives of (— )-tropic acid showed a trend similar to derivatives of l-( + )-lactic acid, the Lg configuration XXIII being tentatively assigned on the basis of molecular rotation. 

In addition to lactic acid producing bacteria, a few mycelial molds belonging to Rhizopus are good lactic acid producers. The ability of Rhizopus to produce only L-(-I-)-lactic acid aerobically under nitrogen-limited environments has been studied [25-28]. Compared to bacterial fermentation, Rhizopus requires only inorganic salts. In addition, Rhizopus cultures are more tolerant to a low pH environment. Consequently, pH maintenance is not as stringent as bacterial culture during lactic acid fermentation. Furthermore, Rhizopus molds are amy-lolytic that can produce lactic acid from starchy materials directly. For example, R. oryzae NRRL 395 was used to ferment starch derived from barley, cassava, corn, oat, and rice to L-lactic acid [25]. 

Lactic acidosis is one of the most common canses of high SAG metabolic acidosis. Lactic acid is the end prodnct of anaerobic metabolism of glucose (glycolysis). In normal individnals, lactic acid derived from pyruvate enters the circulation in small amonnts and is promptly removed by the liver. In the liver, and to a lesser extent in the kidney, lactic acid is reoxidized to pyruvic acid, which is then metabolized to CO2 and H2O. The normal plasma lactate concentration in healthy subjects is approximately 1 rnEq/L. " The diagnosis of lactic acidosis should be considered in aU patients with metabolic acidosis... 

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). 

R)- and (S)-2-Phenyl-l,4-butancdiol (21 and 22) have been prepared from (5)-lactic acid derivatives by the following reaction sequence392. 

Chitosan and its amino acid derivatives (poly D, L-lactic acid) have been explored as an extracellular matrix-like surface to promote cell adhesion and growth [229]. Four kinds of chitosan-amino acid derivatives were prepared to minimize the carbohydrate moieties of cell matrix glycoproteins. 

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. 

Preparation of an useful synthon, the cyclic carbamate of L-daunosaminal (104), was achieved by sequential catalytic transformations of a key intermediate. Suitably protected propargyl diol 101, which was obtained by diastereoselective addition of allenyl stannate 99 to 0-benzyl (S)-lactyl aldehyde 100, was transformed as depicted in Scheme 18. Cycloisomerization to 3-deoxyglycal 103 was achieved by irradiation in the presence of tungsten hexacarbonyl, and subsequent nitrene insertion was catalyzed by rhodium acetate. Overall yield of the bicyclic daunosaminal (104) derivative from lactic acid derivative amounted to 44% [78]. 

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