Pyrimidine-Fused Heterocyclic Frameworks Based on an N4-Arylcytosine Scaffold: Synthesis, Characterization, and PNA Oligomerization of the Fluorescent Cytosine Analogue 5,6-BenzopC

A synthesis of an intrinsically fluorescent
cytosine analogue 5,6-benzopC
has been developed utilizing the reductive Ni-mediated cyclization
of an N4-aryl,N4-(Boc)­cytosine intermediate as a key step. 5,6-BenzopC
was found to possess interesting fluorescence properties (Φ
= 0.79, EtOH; Stoke’s shift 113 nm). Peptide nucleic acid (PNA)
oligomerization of the 5,6-benzopC monomer was carried out, followed
by hybridization studies with complementary deoxyribonucleic acid
(DNA) and ribonucleic acid (RNA) which showed the modification to
be well tolerated in the sequence contexts examined. Initial attempts
to synthesize the heterocyclic skeleton present in 5,6-benzopC resulted
in the discovery of routes to the pyrimido­[1,6-a]­benzimidazole,
pyrimido­[1,6-a]­quinazoline, and pyrimido­[1,6-a]­benzo­[b]­6-bora-1,3-diazine heterocyclic
frameworks.