Synthesis and EPR Studies of 2′‐Deoxyuridines with Alkynyl, Rodlike Linkages

Abstract

Sonogashira coupling of diacetyl 5-ethynyl-2'-deoxyuridine with diacetyl 5-iodo-2'-deoxyuridine gave the acylated ethynediyl-linked 2'-deoxyuridine dimer (3b) (63%) that was deprotected with ammonia/methanol to ethynediyl-linked 2'-deoxyuridines (3a) (79%). Reaction of 5-ethynyl-2'-deoxyuridine (1a) with 5-iodo-2'-deoxyuridine gave the furopyrimidine linked to 2'-deoxyuridine (78%). Catalytic oxidative coupling of 1a (O2, CuI, Pd/C, DMF) gave the butadiynediyl-linked 2'-deoxyuridines (4) (84%). Double Sonogashira coupling of 5-iodo-2'-deoxyuridine with 1,4-bis(ethynyl)benzene gave 1,4-phenylenediethyne-bridged 5-ethynyl-2'-deoxyuridines (5, 83%). Cu-catalyzed cycloisomerization of dimers 4 and 5 gave their furopyrimidine derivatives. One electron addition to 1a, 3a and 4 gave the anion radical whose ESR spectra showed the unpaired electron largely localized at C6 of one uracil ring (17 G doublet) at 77 K. For the ethynediyl- and butadiynyl-linked uridines 3a and 4 the ESR spectra of their one electron oxidized species at 77 K showed that the unpaired electron is delocalized over both rings. Thus structures 3a 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 could separate hole transfer from electron transport between strands in DNA systems. In the crystal structure of acylated dimer 3b the bases were found in the anti position to each other across the ethynyl link. Similar anti conformation was preserved in the derived furopyrimidine–deoxyuridine dinucleoside.

Organometallic Nucleosides: Synthesis and Biological Evaluation of Substituted Dicobalt Hexacarbonyl 2′‐Deoxy‐5‐oxopropynyluridines

“…2′‐Deoxy‐5‐alkynyluridines 9 a – h (Scheme ), containing a conjugated alkyne function, represent versatile materials for reactions that lead, among others, to furopyrimidines, halofuropyrimidines, and alkynyl dimers …”

Labeling of Cellular DNA with a Cyclosal Phosphotriester Pronucleotide Analog of 5‐ethynyl‐2′‐deoxyuridine

“…Compound 4 was prepared from 5‐iodo‐2′‐deoxyuridine and 1,7‐octadiyne also using Sonagashira conditions. The bis‐acetylated compounds 2 and 5 were synthesized from EdU and 4 , respectively, using standard acylation conditions of acetic anhydride in pyridine at room temperature. To synthesize the mono‐acetylated compound 1 , the primary hydroxyl group of EdU was first selectively protected using TBDPSCl, followed by acylation of the 3′‐OH then removal of the TBDPS protecting group using tetrabutylammonium fluoride.…”

Intramolecular cyclizations of functionalized diynes

“…Синтез замещенных фуропиримидинов 32 в присутствии солей меди(I) и основания из соответствующих произ-водных бута-1,3-диина 31 был использован как способ получения модель-ных соединений для изучения биохимических процессов (схема 5) [26].…”