Green enantiomeric separation

JH Shah, GM Swartz, AE Papathanassiu, AM Treston, WE Fogler, JW Madsen, SJ Green. Synthesis and enantiomeric separation of 2-phthalimido-glutaric acid analogues potent inhibitors of tumor metastasis. J Med Chem 42 3012-3017, 1999. 

Host-guest inclusion complexations are usually carried out in organic solvents. As a green process, inclusion complexation can be performed in a water suspension medium or in the solid state. When the solid-state reaction in a water suspension medium is combined with an enantioselective inclusion complexation in the same water medium, a one-pot green preparative method for obtaining optically active compounds can be designed. In all these cases, enantiomers separated as inclusion complexes are recovered by distillation of the inclusion complex. When enantioselective inclusion complexation in the solid state is combined with the distillation technique, a unique green process for enantiomeric separation can result. 

Some enantiomeric separations based on the host-guest inclusion technique have already been described so far in reviews and books [1] and this chapter describes enantiomeric separations summarized from the viewpoint of achieving more green processes. 

Enantiomeric separations of bicyclic acid anhydride 69, lactones 70 and 71 and carboximides 72 and 73 by complexation with la-c in organic solvents were also successful (Table 3.3-3) [26]. These complexations can probably be carried out in a water suspension medium and hence be described as green processes. rac-Panto-lactone (74) was separated to produce (S)-(-)-74 of 99% ee in 30% yield by complexation with Ic [27]. Enantiomerically impure monoterpenes were purified by inclusion complexation with a chiral host compound. For example, (lS,5S)-(-)-verbe-none (75a) of 78% ee gave 99% ee enantiomer by complexation with la. By similar treatment of 75b of 91% ee with la as above, (lR,5R)-(-i-)-75b of 98% ee was obtained [28]. 

Green One-Pot Preparative Process for Obtaining Optically Active Compounds by a Combination of Solid-state Reaction and Enantiomeric Separation in a Water Suspension Medium... 

A new green preparative method for obtaining optically active compounds can be designed using one-pot solid-state reactions and enantiomeric separation processes, carried out continuously in a water suspension medium. Some successful examples are described in this section. 

There is no doubt that enantiomeric separation of racemic compounds will become increasingly important. The enantiomeric separation method should, however, be simple, green and economical. In this chapter, some examples of separations by inclusion complexation with chiral or achiral host compounds are described. In future, chiral host compounds for enantiomeric separation should be improved. More green and cheap chiral sources should be developed for more efficient and safe enantioseparations. For example, naturally occurring chiral sources such as sugars, amino acids, terpenes, alkaloids and cellulose could become useful and important... 

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