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.