Controlling chirality in the synthesis of 4 + 4 diastereomeric amine macrocycles derived from -1,2-diaminocyclopentane and 2,6-diformylpyridine.

A few suitably long dialdehyde and primary diamine building blocks of a predetermined chirality have been designed and synthesized to enable controlled and efficient synthesis of all six possible diastereomers of 4 + 4 macrocyclic amine derived from -1,2-diaminocyclopentane (DACP) and 2,6-diformypyridine (DFP) units. Although two out of six diastereomers have been reported recently, their synthesis presented here is more direct and occurs with an improved yield. This family of 4 + 4 macrocycles contains one pair of homochiral enantiomers of identical and configurations of DACP units, two different forms ( of alternating and of neighboring configuration of DACP moieties) as well as one pair of heterochiral enantiomers, where configuration of one diamine fragment is opposite to the other three diamine parts, and , respectively.