Synthesis and EPR studies of 2'-deoxyuridines with alkynyl, rodlike linkages.
Sonogashira coupling of diacetyl 5-ethynyl-2'-deoxyuridine with diacetyl 5-iodo-2'-deoxyuridine gave the acylated ethynediyl-linked 2'-deoxyuridine dimer (3 b; 63%), which was deprotected with ammonia/methanol to give ethynediyl-linked 2'-deoxyuridines (3 a; 79%). Treatment of 5-ethynyl-2'-deoxyuridine (1 a) with 5-iodo-2'-deoxyuridine gave the furopyrimidine linked to 2'-deoxyuridine (78%). Catalytic oxidative coupling of 1 a (O(2), CuI, Pd/C, N,N-dimethylformamide) gave butadiynediyl-linked 2'-deoxyuridines (4; 84 %). Double Sonogashira coupling of 5-iodo-2'-deoxyuridine with 1,4-diethynylbenzene gave 1,4-phenylenediethynediyl-bridged 2'-deoxyuridines (5; 83%). Cu-catalyzed cycloisomerization of dimers 4 and 5 gave their furopyrimidine derivatives. One-electron addition to 1 a, 3 a, and 4 gave the anion radical, the EPR spectra of which showed that the unpaired electron is largely localized at C6 of one uracil ring (17 G doublet) at 77 K. The EPR spectra of the one-electron-oxidized derivatives of ethynediyl- and butadiynediyl-linked uridines 3 a and 4 at 77 K showed that the unpaired electron is delocalized over both rings. Therefore, structures 3 a and 4 provide an efficient electronic link for hole conduction between the uracil rings. However, for the excess electron, an activation barrier prevents coupling to both rings. These dimeric structures could provide a gate that would separate hole transfer from electron transport between strands in DNA systems. In the crystal structure of acylated dimer 3 b, the bases were found in the anti position relative to each other across the ethynyl link, and similar anti conformation was preserved in the derived furopyrimidine-deoxyuridine dinucleoside.
Sniady
Adam
A
Department of Chemistry and Center for Biomedical Research, Oakland University, 2200 N. Squirrel Rd. Rochester, Michigan 48309-4477, USA.
Sevilla
Michael D
MD
Meneni
Srinivasarao
S
Lis
Tadeusz
T
Szafert
Slawomir
S
Khanduri
Deepthi
D
Finke
John M
JM
Dembinski
Roman
R
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D007454:Iodides / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure
D000480:Alkynes; D003432:Cross-Linking Reagents; D007454:Iodides; D003300:Copper; C073870:cuprous iodide; D004247:DNA; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine