Abstract
In order to develop a range of trianglimine macrocycles with varying functionalities, a novel synthetic approach to trianglimine macrocyclic chemistry has been applied. The chemistry developed has been used to extend versatile applications of the reversible imine bonds exhibited in these structures. Trianglimine macrocycles were synthesised with expanded functionalities, which were used from a medicinal chemists view-point as selective receptors for biological targets within the bacterial cell wall biosynthetic pathway. By using the dynamic combinatorial library (DCL) approach, originally proposed by Sanders and Lehn. A combinatorial library of all the synthesised trianglimine macrocycle was prepared. In order to observe the host guest binding abilities of these macrocycles, the [3+3] cyclocondensation reaction between aromatic dialdehydes and enantiomerially pure C2-symmetrical diamine; diaminocyclohexane was studied. This in all cases produces the desired thermodynamically stable triangular product. These triangular macrocycles, 'trianglimines', were synthesized using the stated methodology to produce compounds with ring sizes of up to 54. These have been used as host guest systems in green chemistry and can now be applied into the medicinal world as potential antibacterial agents. Aromatic dialdehyde trianglimine macrocycles have been designed in order to accommodate oligopeptide binding, via specific binding sites, which are unique within bacterial cell wall synthesis. The functional groups incorporated into the building blocks will offer binding motif for the various functionalities in the oligopeptides (COO-, CONH, NH3+) These functionalities are introduced into the trianglimine ring via the biaryl dialdehyde building blocks. The biaryl ring system used is synthesized in high yield by the Suzuki Miyaura methodology as this method tolerates a wide range of functional groups. The chosen biaryl ring system ensures an enlarged trianglimine cavity. This provides optimal space for potential host binding. In all cases 4,4'-biphenyldialdehydes have been synthesized as previous molecular modelling studies show a preference for this isomer.