Recognition of α-amino acid derivatives by N,N′-dibenzylated S,S-(+)-tetrandrine

Abstract

Complexation of free and N-acetylated α-amino acid anions (Gly, Ala, Phe) and some structurally related guests by a dicationic cyclophane-type N,N′-dibenzylated chiral derivative of a bisisoquinoline macrocyclic alkaloid S,S-(+)-tetrandrine (DBT) has been studied by ¹H-NMR titrations in D₂O. In contrast to other macrocyclic hosts like cyclodextrins and calixarenes, DBT shows highest affinity and large enantioselectivity (K(S)/K(R) ≥ 10) toward smaller N-acetylalanine and binds larger phenylalanine derivatives more weakly and non-selectively. With 1,2,3,4-tetrahydroisoquinoline-3-carboxylate, a rigid analog of phenylalanine, binding again becomes enantioselective with K(S)/K(R) = 3.8. The binding specificity of DBT is rationalized on the basis of molecular mechanics calculations.