Nucleobase-Functionalized 5-Aza-7-deazaguanine Ribo- and 2′-Deoxyribonucleosides: Glycosylation, Pd-Assisted Cross-Coupling, and Photophysical Properties

Abstract

The special nucleobase recognition pattern of 5-aza-7-deazaguanine nucleosides makes them valuable for construction of homo purine DNA, silver-mediated base pairs, and expansion of the four letter genetic coding system. To widen the utility of 5-aza-7-deazaguanine nucleosides, side chains were introduced at position-7 of the nucleobase. As key compounds, 7-iodo nucleosides were synthesized. Nucleobase anion glycosylation of the iodo derivative of isobutyrylated 5-aza-7-deazaguanine with the bromo sugar of 2,3,5-tri-O-benzoyl-1-O-acetyl-d-ribofuranose gave the pure β-D anomeric N-9 glycosylation product (67%), whereas one-pot Vorbrüggen conditions gave only 42% of the iodinated nucleoside. The noniodinated nucleoside was formed in 84%. For the synthesis of 2′-deoxyribonucleosides, anion glycosylation performed with Hoffer’s 2′-deoxyhalogenose yielded an anomeric mixture (α-D = 33% and β-D = 39%) of 2′-deoxyribonucleosides. Various side chain derivatives were prepared from nonprotected nucleosides by Pd-assisted Sonogashira or Suzuki–Miyaura cross-coupling. Among the functionalized ribonucleosides and anomeric 2′-deoxyribonucleosides, some of them showed strong fluorescence. Benzofuran and pyrene derivatives display high quantum yields in non-aqueous solvents and solvatochromism. Single-crystal X-ray analysis of 7-iodo-5-aza-7-deaza-2′-deoxyguanosine displayed intermolecular iodo–oxygen interactions in the crystal and channels filled with solvent molecules.

5‐Aza‐7‐deazaguanine–Isoguanine and Guanine–Isoguanine Base Pairs in Watson–Crick DNA: The Impact of Purine Tracts, Clickable Dendritic Side Chains, and Pyrene Adducts

“…2‐Amino‐8‐[2‐deoxy‐5‐ O ‐(4,4′‐dimethoxytriphenylmethyl)‐β‐ d ‐ erythro ‐pentofuranosyl)]‐6‐iodo‐8 H ‐imidazo[1,2‐ a ]‐ s ‐triazin‐4‐one (8) : From the slower migrating zone, compound 8 was obtained as a colorless foam (660 mg, 37 %). Analytical data were identical to those reported earlier [11b] . TLC (silica gel, CH 2 Cl 2 /MeOH, 95:5): R f =0.3; 1 H NMR (600 MHz, [D 6 ]DMSO, 26 °C): δ =2.22 (ddd, J= 13.4, 6.4, 4.7 Hz, 1 H; C2′‐H α ), 3.12 (ddd, J= 13.6, 10.4, 4.5 Hz, 2 H; 2×C5′‐H), 3.74 (s, 6 H; 2×OCH 3 ), 3.89 (dt, J= 5.7, 3.8 Hz, 1 H; C4′‐H), 4.34 (td, J= 9.0, 4.5 Hz, 1 H; C3′‐H), 5.33 (d, J= 4.5 Hz, 1 H; C3′‐OH), 6.14 (t, J= 6.4 Hz, 1 H; C1′‐H), 6.87 (dd, J= 9.0, 3.1 Hz, 4 H; Ar‐H), 6.99 (d, J= 5.1 Hz, 2 H; NH 2 ), 7.25–7.15 (m, 5 H; Ar‐H), 7.29 (t, J= 7.7 Hz, 2 H; Ar‐H), 7.36 (dd, J= 8.4, 1.2 Hz, 2 H; Ar‐H), 7.42 ppm (s, 1 H; C7‐H); 13 C NMR (151 MHz, [D 6 ]DMSO, 26 °C): δ =38.6 (C‐2′), 55.0 (OCH 3 ), 57.7 (C‐7), 63.8 (C‐5′), 70.0 (C‐3′), 82.7 (C‐1′), 85.5 (C‐4′), 85.7, 113.1 (Ar‐C), 120.8 (C‐8), 126.6 (Ar‐C), 127.6 (Ar‐C), 127.8 (Ar‐C), 129.6 (Ar‐C), 129.6 (Ar‐C), 135.4 (Ar‐C), 135.5 (Ar‐C), 144.8 (Ar‐C), 150.1 (C‐2), 150.6 (C‐4), 158.0 (Ar‐C), 164.2 ppm (C=O); UV/Vis (MeOH): λ max ( ϵ )=267 nm (16 500 mol −1 dm 3 cm −1 ); HRMS (ESI‐TOF): m / z calcd for C 31 H 30 IN 5 NaO 6 + [ M +Na] + : 718.1138; found: 718.1136.…”

“…2‐Amino‐8‐[2‐deoxy‐5‐ O ‐(4,4′‐dimethoxytriphenylmethyl)‐α‐ d ‐ erythro ‐pentofuranosyl)]‐6‐iodo‐8 H ‐imidazo[1,2‐ a ]‐ s ‐triazin‐4‐one (9) : From the faster migrating zone, compound 9 was obtained as a colorless foam (560 mg, 31 %). Analytical data were identical to those reported earlier [11b] . TLC (silica gel, CH 2 Cl 2 /MeOH, 95:5): R f =0.4; 1 H NMR (600 MHz, [D 6 ]DMSO, 26 °C): δ =2.20–2.13 (m, 1 H; C2′‐H β ), 2.71–2.63 (m, 1 H; C2′‐H α ), 2.97 (dd, J= 10.2, 4.6 Hz, 1 H; C5′‐H), 3.09 (dd, J= 10.2, 4.0 Hz, 1 H; C5′‐H), 3.74 (s, 6 H; 2×OCH 3 ), 4.30–4.21 (m, 2 H; C3′‐H, C4′‐H), 3.74 (s, 6 H; 2×OCH 3 ), 5.56 (d, J= 3.4 Hz, 1 H; C3′‐OH), 6.21 (dd, J= 7.8, 2.5 Hz, 1 H; C1′‐H), 6.90 (m, 5 H; Ar‐H, NH 2 ), 7.25–7.21 (m, 5 H; Ar‐H), 7.35–7.30 (m, 2 H; Ar‐H), 7.37 (dd, J= 8.4, 1.2 Hz, 2 H; Ar‐H), 7.63 ppm (s, 1 H; C7‐H); 13 C NMR (151 MHz, [D 6 ]DMSO, 26 °C): δ =40.0 (C‐2′), 55.0 (OCH 3 ), 56.9 (C‐7), 63.8 (C‐5′), 70.9 (C‐3′), 83.9 (C‐1′), 85.6 (quat.…”

“…Direct purification was not possible due to the identical chromatographic mobility of the anomers. Afterwards, Sonogashira cross‐coupling reactions were performed to introduce various side chains [11b, c] . Now, the separation of anomers was improved.…”

Control of Intermolecular Photoinduced Electron Transfer in Deoxyadenosine‐Based Fluorescent Probes

“…Will through‐bound electron transfer be competitive in this case? [49, 50] Incorporation of MFCA and MTCA into double‐stranded DNA may help to answer this question because adjacent natural nucleobases should shield the 7 dA base from complex formation while exposing the electronically coupled chromone to the major groove and water [51] . In the light of our results, it would be interesting to know if formation of poorly emissive charge‐transfer complexes is particular to our compounds or more common to donor electronically coupled to acceptor [52–54] . Addressing this question could help reconsidering conjugates that may have been eliminated too quickly as fluorescent probes of biomolecular structures and interactions.…”

“…[51] In the light of our results, it would be interesting to knowi ff ormation of poorly emissive chargetransfer complexesi sp articular to our compounds or more common to donor electronically coupled to acceptor. [52][53][54] Ad- Figure 8. Schematic representation illustrating the formation of ground-state complexesf avorable only for MFCA and MTCA,PET and radicali on pair products.…”