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,
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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
4OH. 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
31P{
1H} and
195Pt NMR. Complexes
2,
3,
5,
6 and
7 induce a decrease of
1JPt,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.
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