C-nucleoside studies. Part 21. Synthesis of some hydroxyalkylated pyrroloand thieno-[3,2-d]pyrimidines related to known antiviral acyclonucleosides

Abstract

Treatment of (S)-4,5-isopropylidenedioxypentanonitrile 17 with ethyl formate and sodium hydride gave a hydroxymethylene derivative which interacted with aminoacetonitrile to give 3-cyanomethyleneamin-2-[(S)-isopropylidenedioxypropyl]acrylonitrile 19; this was elaborated via 3-amino-2-cyano-4-[(S)-2,3-isopropylidenedioxypropyl]pyrrole 22 into 4-amino-7-[(S)-2,3-dihydroxypropyl]pyrrolo[3,2-d]pyrimidine 9. Treatment of the hydroxymethylene derivative of 17 with methanesulphonyl chloride, followed by acetylthioacetonitrile and sodium carbonate in ethanol gave 3-amino-2-cyano-4-[(S)-2,3-isopropylidenedioxypropyl]thiophene 25, convertible in two steps into 4-amino-7-[(S)-2,3-dihydroxypropyl]thieno[3,2-d]pyrimidine 10.

Similar chemistry was employed for the conversion of 5,6-isopropylidenedioxyhexanonitrile 30 into the higher homologues 4-amino-7-(3,4-dihydroxybutyl)pyrrol- and thieno-[3,2-d]pyrimidine 11 and 12, and for the preparation of 4-amino-7-(4-hydroxy-3-hydroxymethylbutyl)pyrrolo[3,2-d]pyrimidine 13d from 6-benzylox-5-benzyloxymethylhexanonitrile 41. The hydroxyalkylated products 9–13 are C-nucleoside analogues of known antiviral agents, but did not display antiviral activity.