Mechanistic studies in the synthesis of a series of thieno-expanded xanthosine and guanosine nucleosides

During the synthetic pursuit of guanosine (tri-G) and xanthosine (tri-X) tricyclic nucleosides analogues, an interesting side product was discovered. In an effort to uncover the mechanistic factors leading to this result, a series of reaction conditions were investigated. It was found that by varying the conditions, the appearance of the side product could be controlled. In addition, the yield of the desired products could be manipulated to afford either a 50:50 mix of both tri-G and tri-X, or a majority of one or the other. To demonstrate the broad utility of the method, it was also adapted to the synthesis of guanosine and xanthosine from 5-amino-1-β-d-ribofuranosyl-4-imidazolecarboxyamide (AICAR). The mechanistic details surrounding the synthetic efforts are reported herein.