Investigations of new synthetic approaches to imidazo[4,5-e]-1,2,4-triazine (6-azapurine) and pyrimido[4,5-e]-1,2,4-triazine (6-azapteridine) derivatives and related polyaza heterocycles

• Main Author: Mackenzie, Linda
• Published: University of Edinburgh 1991
• Subjects: 547.59
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.654290

This thesis is concerned with the development of new, general, synthetic approaches to aza- and deaza-aza- pteridines and purines of potential biological interest. The construction of derivatives of four such ring systems, all containing a 1,2,4-triazine nucleus was studied. In the case of 6-aza-1-deaza-pterine synthesis, annulation of the appropriate bicyclic 1,2,3-triazolo-[1,-PROB*LEM]-1,2,4-triazine derivatives afforded the corresponding 1,2,3-triazolo[1,5-PROB*LEM]-pyrido[4,3-PROB*LEM]-1,2,4-triazines. The latter underwent smooth acid-catalysed triazole scission providing a general route to variously functionalised pyrido[4,3-PROB*LEM]-1,2,4-triazine (6-aza-1-deazapteridine) derivatives. Syntheses of the two classes of aza- and aza-deaza-purines investigated were based on a common type of 1,2,3-triazolo[1,5-PROB*LEM]-1,2,,4-triazine intermediate, bearing a readily displaceable benzenesulphonyl moiety <i>ortho</i> to an amino- group in the triazine ring. The construction of 6-azapurines was approached by nucleophilic displacement of the benzenesulphonyl group with cyanamide anion with concomitant cyclisation of the resulting <i>ortho</i>-amino cyanamide products giving the corresponding tricyclic 1,2,3-triazolo[1,5-PROB*LEM] imidazo[4,5-PROB*LEM]-1,2,4-triazine derivatives. However, attempts to obtain molecules of the latter type appropriate for acid-catalysed triazole scission to imidazo[[4,5-PROB*LEM]-1,2,4-triazines (6-azapurines) were unsuccessful. Synthesis of 6-aza-7-deaza-purines used a similar approach to that investigated for 6-azapurines, namely nucelophilic displacement of the benzenesulphonyl group in <i>ortho</i>-benzenesulphonyl 1,2,3-triazolo[1,5-PROB*LEM]-1,2,4-triazine derivatives but using stabilised carbanions rather than amide ions. Acid-catalysed triazole scission of the resulting tricyclic 1,2,3,-triazolo[1,,5-PROB*LEM]-pyrrolo[2,3-PROB*LEM]-1,2,4-trizine derivatives then afforded a new and potentially general route to pyrrolo[2,3-PROB*LEM]-1,2,4-triazine (6-aza-7-deazapurine) derivatives.