SYNTHESIS OF SOME NEW THIENO[3,4-D]PYRIMIDINES AND THEIR C-NUCLEOSIDES

The synthesis of several new thieno[3,4-d]pyrimidine C-nucleosides 5-8 is described. The known 5-ribosylated methyl 4-(formylamino)thiophene -3-carboxylate key intermediate 20 was obtained as a mixture of anomer s in significantly improved yield by condensation of the sugar 15 with methyl 4-(formylamino)thio-phene-3-carboxylate 19 in nitromethane at 60-degrees in the presence of stannic chloride. Attempts to prepare th e C-7 ribosylated compound 21beta by direct condensation of the bicycl ic base 10 with 15 gave instead the N-I ribosylated nucleoside 16. The synthesis of the corresponding and previously unknown thieno[3,4-d]py rimidine bases 12 and 13 is described along with stability studies on the 4-methylthio derivative 12. Preliminary biological studies indicat e that adenosine analogue 7 is a potent growth inhibitor of several ma mmalian tumor cell lines.