Its Enantioresolution with Natural - -Menthol

Facile Synthesis of MaNP Acid (3) and Its Enantioresolution with Natural (-)-Menthol [40, 42, 50] 

To synthesize a large amount of enantiopure chiral MaNP acid (3), the facile synthesis and enantioresolution of racemic acid 3 were carried out as shown in Fig. 9.9. In general, for enantioresolution of carboxylic acids, chiral synthetic amines or alkaloids have been used. However, we have adopted the following novel strategy using chiral alcohols chiral alcohols are condensed with racemic acid 3 and the diastereomeric esters formed are separated by HPLC on silica gel. 

The separated esters are then hydrolyzed to yield both enantiomers of the desired carboxylic acids 3. 

As a chiral alcohol, naturally occurring (-)-menthol was selected and esterified with racemic acid 3. It was surprising that the diastereomeric esters 47a and 47b formed were very easily separated by HPLC on silica gel (hexane/EtOAc =10 1) as illustrated in Fig. 9.10. The separation and resolution factors were extraordinarily high (a = 1.83, = 4.55), indicating that acid 3 has great ability to recognize 

The NMR Anisotropy Method for Determining the Absolute Configuration of Secondary Alcohols the Sector Rule and Applications [42, 50] 

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