Platelet aggregation inhibitors. IX. Chemical transformation of adenosine into 2-thioadenosine derivatives.

A facile synthesis of 2-thioadenosine (IX) and its derivatives from adenosine (I) was described. Treatment of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide O-benzyloxime (IV), obtained via 3 steps from I, with CS2-MeOH-pyridine at room temperature gave N1-benzyloxy-2-thioadenosine (VII) which was readily transformed into 2-benzylthioadenosine N-oxide (VIII) by heating. Treatment of IV with CS2-MeOH-NaOH at 180°in an autoclave gave a mixture of 2-thioadenosine (IX), 2-methylthioadenosine (X) and 2-benzylthioadenosine (XI). Reaction of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamidoxime (XV) obtained from I with CS2-MeOH-H2O at 120°in an autoclave gave IX in an overall yield of 60% (practically 2 steps). Treatment of XV with CS2-MeOH-pyridine at room temperature yielded 2-thioadenosine N-oxide (XVIII) which was subsequently transformed into IX by H2S. Adenines (XX) were also transformed into 2-thioadenine or 9-benzyl-2-thioadenine (XXV) by treatment of the intermediate compounds (XXII) of carboxamidoxime-type with CS2-MeOH-H2O at 120°.