The synthesis, NMR, and conformational studies of purinophanes and approaches towards the synthesis of pyrimidinophanes

Abstract

<p>In an effort to investigate the magnetic effects exerted by the heterobases found in ribo- and deoxyribonucleic acids, work has been directed towards the synthesis of purine and pyrimidine cyclophanes. The bridging methylene protons act as "reporter" groups of the magnetic environment of these systems furnishing values for the spatial definition of the diamagnetic susceptibility anisotropy and supplying a viable means of appraising the existing theoretical models. (8) -(N6,9)-6-Aminopurinophane (1) (an adenine based cyclophane) was the first to be prepared in our laboratory. Its nonamethylene (2) and decamethylene (3) homologs have also been synthesized using nucleophilic aromatic substitution for bridge attachment at the 6-position and the Mitsunobu reaction for alkylation at the 9-site. Both the C9 and C10 cyclophanes have been investigated using NMR spectroscopy while the structure of (9) -(N6,9)-6-Aminopurinophane has been determined using X-ray crystallography. Many of the interesting fluxional properties of the purinophane series result from restricted rotation about the N6-C6 bond and manifest themselves in the variable temperature NMR. UV spectroscopy has been used to provide further insight into the conformational properties of these molecules. The "Intact Bridge Attachment" and "Bridge Formation via Coupling" approaches to cyclophane formation have been applied towards the synthesis of the pyrimidinophane. (9) -(1,N4)-4-amino-2-one-pyrimidinophane (4) (a cytosine based cyclophane). Unfortunately, repeated attempts failed to produce the desired target molecule. The problems associated with each approach will be discussed. A semi-empirical model developed for calculation of the chemical shifts of the bridge protons in the (n) -(N6,9)-6-aminopurinophane series proved to be an effective tool for anisotropy mapping.</p>