Mandelic acid stereochemistry

The stereochemical aspects of the fates of 1-phenyl-1,2-ethanediol and mandelic acid in rats have been examined by Drummond et al. (1990). The proportions of a dose of 1-phenyl-1,2-ethanediol converted to phenylglyoxylic and mandelic acids depend upon its stereochemistry. The i -diol is preferentially converted to i -mandelic acid (30% of the dose in 48 h) with 15% of the dose as phenylglyoxylic acid. In contrast, after administration of the 5 -diol, the major product is phenylglyoxylic acid (46% of the dose) with 16% as mandelic acid (JUS 80 20). 

Equation B5.6 depicts the reaction of an achiral aldehyde with a homochiral boron enolate derived from (5)-mandelic acid. Again the geometry of the enolate controls the relative stereochemistry of C2 and C3 and so only the two erythro isomers are formed. In this case, however, the homochiral centre in the boron enolate results in approach to one face of the aldehyde being strongly preferred over approach to the other face and a product ratio of 2R,3S 2S,3R = 28 1 is observed. 

If the boron enolate derived from (/ )-mandelic acid is used in Equation B5.6 then a reversal of selectivity to 2R,3S 2S,3R — 1 28 is anticipated. Thus, on combination of the (/ )-boron enolate with (-)-dimethylglutaric hemialdehyde, the stereochemical preferences of the two reagents work against each other (they are said to be mismatched ) and relatively low stereoselectivity is observed. The stereochemistry of the major diastereoisomer is that produced by the partner with the strongest control over the reaction (Equation B5.8). 

In the following reaction sequence, the stereochemistry of mandelic acid is transmitted to a new hydroxy-acid by stereochemically controlled reactions. Give mechanisms for each reaction and state whether it is stereospecific or stereoselective. Offer some rationalization for the creation of new stereogenic centres in the first and last reactions. 

If we repeat this reaction, this time using an enantiomerically pure sample of the acid, available from (Jl)-mandelic acid, the almond extract you met on p. 310, we will again get two diastereoisomeric products, but this time each one will be enantiomerically pure. Note that the stereochemistry shown here is absolute stereochemistry. 

The use of a disubstituted amino alcohol in cleft-Uke derivatives 32 (Fig. 9) was recently described as an efficient strategy for obtaining very high enantioselectivity (ef= 11.2 for mandelic acid enantiomers) [72]. This system was shown to act with different mechanisms according to its stereochemistry, since one of the two enantiomers induced recovery of fluorescence of the binaphthyl group, while the other was shown to induce exciplex formation, quenching the fluorescence of the monomeric fluorophore. 

Enzymatic enantioselectivity in organic solvents can be markedly enhanced by temporarily enlarging the substrate via salt formation (Ke, 1999). In addition to its size, the stereochemistry of the counterion can greatly affect the enantioselectivity enhancement (Shin, 2000). In the Pseudomonas cepacia lipase-catalyzed propanolysis of phenylalanine methyl ester (Phe-OMe) in anhydrous acetonitrile, the E value of 5.8 doubled when the Phe-OMe/(S)-mandelate salt was used as a substrate instead of the free ester, and rose sevenfold with (K)-maridelic acid as a Briansted-Lewis acid. Similar effects were observed with other bulky, but not with petite, counterions. The greatest enhancement was afforded by 10-camphorsulfonic acid the E value increased to 18 2 for a salt with its K-enanliomer and jumped to 53 4 for the S. These effects, also observed in other solvents, were explained by means of structure-based molecular modeling of the lipase-bound transition states of the substrate enantiomers and their diastereomeric salts. 

Hou reported (23) that Flavobacterium sp. DS5 converted oleic acid to 10-KSA in 85% yield. Optimum time, pH, and temperature for the production of 10-KSA are as follows 36 h, 7.5, and 30°C. Asmall amount of 10-HSA( 10% ofthe main product 10-KSA) is also produced during the bioconversion. 10-KSA is not further metabolized by strain DS5 and accumulates in the medium. In contrast to growing cells, a resting cell suspension of strain DS5 produces 10-HSA and 10-KSA in a ratio of 1 3. The cell-free crude extract obtained from ultrasonic disruption of the cells converts oleic acid mainly to 10-HSA (10-HSA 10-KSA = 97 3). This result strongly suggested that oleic acid is converted to 10-KSA via 10-HSA. Stereochemistry of 10-HSA from strain DS5, determined by H NMR ofthe mandelate esters, showed 66% enantiomeric excess in 10(7 ) form. 

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