C-NUCLEOSIDE STUDIES .21. SYNTHESIS OF SOME HYDROXYALKYLATED PYRROLO[3,2-D]PYRIMIDINES AND THIENO-[3,2-D]PYRIMIDINES RELATED TO KNOWN ANTIVIRAL ACYCLONUCLEOSIDES

Treatment of (S)-4,5-isopropylidenedioxypentanonitrile 17 with ethyl formate and sodium hydride gave a hydroxymethylene derivative which interacted with aminoacetonitrile to give 3-cyano-methyleneamino-2-[(S)-isopropylidenedioxypropyl]acrylonitile 19; this was elaborated via 3-amino-2-cyano-4-[(S)-2,3-isopropylidenedioxypropyl]pyrrole 22 into 4-amino-7-[(S)-2,3-dihydroxy-propyl]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)pyrrolo- 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 13 from 6-benzyloxy-5-benzyloxymethylhexanonitrile 41. The hydroxyalkylated products 9-13 are C-nucleoside analogues of known antiviral agents, but did not display antiviral activity.