| Classic PAMAM dendrimers have been constructed from a single point on a pyridoxamine core and terminated with enantiopure N,N-dimethylphenylalanine. Transamination to form phenylalanine and alanine from their related keto acids produced enantioselectivities, induced by the formally remote chiral caps, supporting a computer model that indicates folding of the dendrimer chains back into the core region.;A more detailed study about converting an aryl aldehyde to its primary amine derivative under neutral conditions via decarboxylative transamination has been conducted. This novel methodology applies to a variety of substrates with electron donating as well as withdrawing groups.;Finally, a promising chiral camphor-based pyridoxamine derivative was proposed to achieve high enantioselectivity in transamination. The challenge of synthesis of such a compound was featured as establishing a basic side arm, and installing the pyridine ring with the correct functional groups. Starting with the side arm, a reasonable synthetic plan was carried out in eleven steps until the crowd at the side arm prohibited further elaboration of the pyridine ring. Therefore setting up the pyridine ring was completed prior to the side arm. The steric effect was overcome by a novel Michael reaction with a doubly activated Michael acceptor. After the required carbon scaffold was set up, the desired pyridine was finally synthesized. Further work to install the functional substituents on the pyridine ring and elaboration over the side arm will be needed.;Next, another series of PAMAM dendrimers have been synthesized from two opposite sites on a pyridoxamine core and capped with chirally terminal amino groups. The observed catalysis and chiral induction by formally further away residues, coupled with our previous results, demonstrate that even a dendrimer with catalytic groups formally remote from the pyridoxamine unit is a good mimic of some aspects of transaminase enzymes. Our new dendrimers synthesized via two starting points support the dense core model of dendrimer structures in solution, where the flexible chains can fold back to fill otherwise empty space. |
