Atrolactic acid method

Fig. 2. Atrolactic acid method for the correlation of configuration, methyl group is added from the least hindered side of carbonyl.

The synthesis of atrolactic acid through acetophenone cyanohydrin was first described by Spiegel12 and has since been used by several other investigators.6-13-17 The above preparation is adapted from the methods of McKenzie and Clough16 and Freudenberg, Todd, and Seidler.17... 

The esters of the optically active alcohols with a-oxobenzeneacetic acid, 18 or ent- 18, are treated with methylmagnesium iodide to give in a diastereoselective reaction two atrolactic acid esters, one of which prevails. The mixture of esters is then hydrolyzed (of course, quantitative hydrolysis is necessary ) and the configuration of the excess atrolactic acid enantiomer (+ )-( )-23 or (-)-(R)-23 is determined by an appropriate method (optical rotation, NMR in the presence of optically active shift reagents or solvents, GLC. of diastereomeric derivatives). 

The structure and absolute stereochemistry of yohimbine (V) have been known for some time (Volume VII, p. 50). The absolute configuration at C-17 has been determined by the method of Prelog, as follows the phenylglyoxalate of yohimbine (VI), on treatment with methyl magnesium bromide, generated an ester (VII) which on hydrolysis gave a substantial yield of L-( + )-atrolactic acid (VIII) (3). 

Mackenzie and Wood obtained low yields by this method, which is the basis of both the Miiller and Wislicenus processes, and recommended instead the hydrolysis of acetophenonecyanohydrin (X) into atrolactic acid (XI), conversion of the latter by distillation under reduced pressure into atropic acid (XII), which was then treated in ethereal solution with hydrochloric acid and the halogen in the resulting j8-chlorohydratropic acid replaced by hydroxyl, by boiling the acid with aqueous sodium carbonate solution, giving tropic acid (XIII), thus ... 

A method for the enantioseparation of atrolactic acids has been presented. HPLC is used with sulfobutyl ether-jS-cyclodextrin as a chiral mobile phase additive and a C18 reversed phase column (41). 

Atrolactic acid is also addressed as 2-hydroxy-2-phenylpropionic acid or a-methylmandelic acid and shown in Figure 1.15. The configuration of atrolactic acid and methods of synthesis and reactions have been described (42). 

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