Lactic acid stereochemistry

We ll see in Section 21.3 that carboxylic acids (RCO2H) react with alcohols (R OH) to form esters (RC02R )- Suppose that ( )-lactic acid reacts with CH3OH to form the ester, methyl lactate. What stereochemistry would you expect the product(s) to have What is the relationship of the products ... 

Problem 9.25 Lactic acid buildup in tired muscles results from reduction of pyruvate. If the reaction occurs from the Re face, what is the stereochemistry of the product ... 

As we have seen a stereoselective reaction is one in which there is a preponderance of one isomer irrespective of the stereochemistry of the reactant. The enzymatic reduction of pyruvic acid is stereoselective when the chiral molecules of the enzyme complexes with achiral pyruvic acid, they given a preponderance of one form of pyruvic acid-enzyme complex which then gives a single form of lactic acid. 

Investigations on the stereochemistry of chiral semiochemicals may be carried out by (gas) chromatographic separation of stereoisomers using chiral stationary phases, e.g. modified cyclodextrins [32]. Alter natively, formation of diastereomers (e.g. Mosher s ester or derivatives involving lactic acid etc.) may be followed by separation on conventional achiral stationary phases. Assignment of the absolute configuration of the natural product will again need comparison with an authentic (synthetic) reference sample. 

The lactic acid, which initiates the reaction sequence. S -lactic acid —> acetal A — enolate B —> acetal C —> R hydroxy carboxylic acid D, has a stereocenter with a well-defined absolute configuration that is destroyed in the enolate intermediate B, but finally restored in the hydroxycarboxylic acid C. This is why the principle concerning the stereochemistry of the key step ( acetal A —> enolate B —> acetal C) is referred to as the self-reproduction of chirality. ... 

If, on the other hand, the reaction is run using Ag20 and a low concentration of sodium hydroxide, (S)-lactic acid is obtained—there is overall retention of stereochemistry. 

The proof of configuration just described relies on the assumption that there is the same relative stereochemistry for the hydrogen atoms in glycolic acid and lactic acid on formation of the enzyme-substrate complexes. The absolute configuration of the glycolate-2-d (22) prepared by reduction of glyoxylate-2-d (21) with glycolate dehydro-... 

Suppose that (S)-lactic acid reacts with (R)-2-butanol to form an ester (Problem 9.70). What stereochemistry would you expect the producWs) to have Draw the reactants and produces). 

Synthetic polymers applied in everyday life rarely possess well-defined stereochemistries of their backbones. This sharply contrasts with the polymers made by Nature where perfect control is the norm. An exception is poly-L-lactide this polyester is frequently used in a variety of biomedical applications. By simply playing with the stereochemistry of the backbone, properties ranging from a semi-ciystalline, high melting polymer (poly-L-lactide) to an amorphous high Tg polymer (poly-mes o-lactide) can be achieved. The synthetic synthesis of such chiral polymers typically starts from optically pure monomers obtained form the chiral pool. The fermentation product L-lactic acid, for example, is the starting material for the synthesis of poly(L-lactide). 

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-... 

PLA properties are strongly dependent on their molecular weight [10] and stereochemistry, being L- and D-lactic acid content [39]. Indeed a PLLA or PDLA homopolymer can develop a crystalline structure whereas an atactic polymer whose L-lactic acid content is below 93% remains amorphous. Consequently, the polymer structure, crystalline or amorphous form, can be at the origin of modification in the thermal, optical, physical, mechanical, and barrier properties of PLA. 

Inversion of the hydroxyl center with oxygen nucleophiles allows one to gain access to R) lactic acid derivatives. This strategy has been used to establish the correct stereochemistry in the alkylidene side chain of pumiliotoxin B (108) [37], a cardiac agent isolated from the Panamanian poison frog (Scheme 16). In the key reaction, conversion of 2 to R)-p-nitrobenzoyl ester 104 proceeds in high yield and with essentially complete inversion of configuration. 

The synthesis is completed by Wittig olefination followed by hexakis( er butylisoni-trile)molybdenum-catalyzed elimination of the pivalate to give 207 in 21% overall yield for the six step sequence. The strategy in this synthesis takes advantage of the chirality of the lactic acid to control stereochemistry in the aldol condensation, and it also furnishes the handle to introduce the final unsaturation. 

Wittig reaction affords intermediate 225, which is elaborated to tetraene 226 in 7 steps. The natural stereochemistry can be obtained by beginning the synthesis with D-lactic acid. 

In the key reaction, a [3,3] rearrangement of trifluoroacetimidate 432 provides allylic amine 433 as a single diastereomer. After protecting-group adjustment, ozonolysis of the olefin, and oxidation of the aldehyde to acid, hydrolysis of all the protecting groups under acidic conditions furnishes the desired product [135]. The sole function of the lactic acid, whose carbon skeleton is removed by the ozonolysis, is to ensure the appropriate stereochemistry of the amino group. 

The doublet structure of the methyl signal at 17 ppm is caused by the stereochemistry. Polylactides, not yet described in any pharmacopoeias, are rather new biodegradable polyesters derived from the chiral lactic acid and used, e. g., in drug delivery systems. The stereochemistry of the polymer is important to the physical and chemical behavior, especially the polymer properties. Pure tactic polymerization can be differentiated from atactic or mixed polymers by simple comparison of the C NMR spectra (Figure 3-10) [4]. 

Enantiomerically pure (H)-2-bromopropanoic acid reacts with concentrated sodium hydroxide to give (S)-lactic acid. The reaction goes with inversion and is a typical Sn2 reaction—and a good one too, since the reaction centre is adjacent to a carbonyl group (see Chapter 15). If, on the other hand, the reaction is run using Ag20 and a low concentration of sodium hydroxide, (k)-lactic acid is obtained—there is overall retention of stereochemistry. 

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