Synthesis of certain [6:5:6] linear tricyclic nucleosides as potential antitumor agents.

Abstract

A new class of tricyclic nucleosides in which the aglycon has a linear [6:5:6] geometry has been synthesized using certain pyrrolo[2,3-d]pyrimidine nucleosides as the starting materials. An adenosine-adenosine analogue (12) has been prepared from 6-aminotoyocamycin using two different synthetic routes. An adenosine-guanosine analogue (4) and several adenosine-6-mercaptopurine ribonucleoside-type tricyclic nucleoside derivatives have also been synthesized. Structural assignments have been based on 1H NMR spectral studies, as well as an unequivocal chemical proof of structure. An interesting chemical shift for the 2' hydrogen of certain tricyclic nucleosides was observed and is discussed. The in vitro cytotoxicity of these nucleosides against leukemia L-1210 has been determined. The in vivo evaluation of these tricyclic nucleosides against mouse leukemia will also be discussed.