Diaza macrocyclic polyethers

Chirality derived from the readily accessible a-amino acids has been incorporated into the side chains of aza and diaza macrocyclic polyethers. A number of procedures suitable for peptide synthesis have proved (178) to be unsuitable for acylating the relatively unreactive secondary amine groups of aza crown ethers. Eventually, it was discovered that mixed anhydrides of diphenylphos-phinic acid and alkoxycarbonyl-L-alanine derivatives do yield amides, which can be reduced to the corresponding amines, e.g., l-172. By contrast, the corresponding bisamides of diaza-15-crown-S derivatives could not be reduced and so an alternative approach, involving the use of chiral A-chloroacetamido alcohols derived from a-amino acids, has been employed (178) in the synthesis of chiral receptors, such as ll-173 to ll-175, based on this constitution. 

During the past two decades, a relatively few macrocyclic polyethers have played central roles in numerous research programs. Examples are 18-crown-6, dibenzo-18-crown-6, and aza-15-crown-5. 4,13-D1aza-18-crown-6 and its derivatives are compounds of considerable current interest despite the parent s high price and limited availability. 4,13-Diaza-18-crown-6 is a key compound in the study of two-armed macrocycles since it may readily be alkylated or acylated to afford a variety of symmetrical, N,N -disubstituted derivatives. 

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