The asymmetric synthesis and conformational analysis of new C₂-symmetric macrocycles derived from head-to-head linked α-amino acids and benzene or pyridine

The synthesis of several novel 15-18-membered macrocycles containing 1,3-disubstituted benzene or 2,6-disubstituted pyridine in a chiral environment is described. The syntheses used a series of di(N^a-tosyl-L-alanylamido)alkanes, which could be prepared in good yield. The macrocyclisation reaction with 1,3-di(bromomethyl)benzene or 2,6-di(bromomethyl)pyridine was facilitated by the use of caesium carbonate as base, and NMR and molecular modelling were used to study the preferred conformations of the macrocycles. © 2001 Elsevier Science Ltd.