Tubercidin

Cyclic ADP-carbocyclic-ribose (cADPcR, 3) is a biologically and chemically stable equivalent of cyclic ADP-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. We became interested in the biological activity of the 7-deaza analogues of cADPcR, i.e., 7-deaza-cADPcR (7) and its 7-bromo derivative, i.e., 7-deaza-7-Br-cADPcR (8), because 7-deazaadenosine is an efficient bioisostere of adenosine. The synthesis of 7 and 8 required us to construct the key N1-carbocyclic-ribosyl-7-deazaadenosine structure. Therefore, we developed a general method for preparing N1-substituted 7-deazaadenosines by condensing a 2,3-disubstituted pyrrole nucleoside with amines. Using this method, we prepared the N1-carbocyclic ribosyl 7-deazaadenosine derivative 10a, from which we then synthesized the target 7-deaza-cADPcR (7) via an Ag(+)-promoted intramolecular condensation to construct the 18-membered pyrophosphate ring structure. The corresponding 7-bromo derivative 8, which was the first analogue of cADPR with a substitution at the 7-position, was similarly synthesized.

C-modified 7-deazaadenosines containing a diphenylacetylene moiety have been synthesised using cross-coupling approaches. The C-modified nucleosides exhibit remarkable fluorescence properties, including high quantum yields. Solvatochromic studies show a near linear correlation between the Stokes shift and solvent polarity which is indicative of intramolecular charge transfer. DFT calculations have allowed us to correlate the experimentally observed photophysical properties with the calculated HOMO-LUMO energy gaps within a series of real and model compounds.

An environmentally sensitive fluorescent nucleoside containing a 3-deazaadenine skeleton has been developed, and its photophysical properties were investigated. Newly developed C3-naphthylethynylated 3-deaza-2'-deoxyadenosine ((3nz) A, 1) exhibited dual fluorescence emission from an intramolecular charge-transfer state and a locally excited state, depending upon molecular coplanarity. DNA probes containing 1 clearly discriminated a perfectly matched thymine base on the complementary strand by a distinct change in emission wavelength.

The title compound {systematic name: 4-amino-5-cyclopropyl-7-(2-deoxy-β-D-erythro-pentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine}, C14H18N4O3, exhibits an anti glycosylic bond conformation, with the torsion angle χ = -108.7 (2)°. The furanose group shows a twisted C1'-exo sugar pucker (S-type), with P = 120.0 (2)° and τm = 40.4 (1)°. The orientation of the exocyclic C4'-C5' bond is -ap (trans), with the torsion angle γ = -167.1 (2)°. The cyclopropyl substituent points away from the nucleobase (anti orientation). Within the three-dimensional extended crystal structure, the individual molecules are stacked and arranged into layers, which are highly ordered and stabilized by hydrogen bonding. The O atom of the exocyclic 5'-hydroxy group of the sugar residue acts as an acceptor, forming a bifurcated hydrogen bond to the amino groups of two different neighbouring molecules. By this means, four neighbouring molecules form a rhomboidal arrangement of two bifurcated hydrogen bonds involving two amino groups and two O5' atoms of the sugar residues.