Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine

Organometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based on adenosine were synthesized, namely N-heterocyclic carbenes bearing a protected and unprotected ribose ring. Reaction of the 8-bromo-2′,3′,5′-tri-O-acetyladenosine with Pt(PPh(3))(4) by C8−Br oxidative addition yielded complex 1, with a Pt(II) centre bonded to C-8 and an unprotonated N7. Complex 1 reacted at N7 with HBF(4) or methyl iodide, yielding protic carbene 2 or methyl carbene 3, respectively. Deprotection of 1 to yield 4 was achieved with NH(4)OH. Deprotected compound 4 reacted at N7 with HCl solutions to yield protic NHC 5 or with methyl iodide yielding methyl carbene 6. Protic N-heterocyclic carbene 5 is not stable in DMSO solutions leading to the formation of compound 7, in which a bromide was replaced by chloride. The cis-influence of complexes 1–7 was examined by (31)P{(1)H} and (195)Pt NMR. Complexes 2, 3, 5, 6 and 7 induce a decrease of (1)J(Pt,P) of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in 1 and 4.