2-aminopyridine nucleosides

As already described for the all-carbon-Diels-Alder reaction, a hetero-Diels-Alder reaction can also be followed by a retro-hetero-Diels-Alder reaction. This type of process, which has long been known, is especially useful for the synthesis of heterocyclic compounds. Sanchez and coworkers described the synthesis of 2-aminopyridines [48] and 2-glycosylaminopyridines 4-144 [49] by a hetero-Diels-Alder reaction of pyrimidines as 4-143 with dimethyl acetylenedicarboxylate followed by extrusion of methyl isocyanate to give the desired compounds (Scheme 4.30). This approach represents a new method for the synthesis of 2-aminopyridine nucleoside analogues. In addition to the pyridines 4-144, small amounts of pyrimidine derivatives are formed by a Michael-type addition. 

The two C-nucleosides derived from 2-aminopyridine (144) and 2-aminopyrimidine (145) have been used to enhance base triplets involving C-G and G-C base pairs. 2-Aminopyridine, which has a pXa of 6.8, was shown to recognise the dG-dC base pair better than dC-dG, whilst 2-aminopyrimidine, with a pXa of 3.3, forms more stable triplets with dC-dG. 

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