Reaction of oxo-oxmium(VI)-pyridine complexes with thymine glycols

Abstract

Grignard reagent obtained from 250 mmol of allyl chloride. The crude product was purified by chromatography on a silica gel column using benzene as the eluent: nmr (CDCL) S 7.4-7.0 (m, 5), 5.9-4.7 (m, 6), 2.50 (m, 4), and 2.14 (s, 1). To 2.96 g (15.8 mmol) of this alcohol in 25 ml of acetonitrile was added 18.95 g (34.6 mmol) of CAN in 20 ml of acetonitrile and 5 ml of water at 80°. After 10 min the initially formed deep red color faded to a light yellow. The mixture was cooled and 50 ml of water and 50 ml of ether were added. The ether layer was separated, washed with saturated NaCl solution, dried (MgS04), and concentrated. Distillation gave 3.7 mmol (23% yield) of a yellowish oil: bp 59-63°( 0.04 mm) [lit.6 bp 100-102°(0.5 mm)]; nmr (CDC1,) S 8.1-7.8 (m, 2), 7.6-7.2 (m, 5), 6.4-6.9 (m, 3), and 3.60 (m, 2).Oxidation Procedure.-Typically, 0.625 mmol of the alcohol, 7.50 mmol of acetonitrile, and 1.25 ml of water were added to a flask equipped with a condenser and magnetic stirring bar. A quantity of 1.25 ml of 1.00 M CAN was added, the flask was immersed in an oil bath at 80°, and the solution was stirred.In the case of 1 and 2 an initial dark red color formed which faded to a light yellow after 4 min. In the case of 3 the initial color was bright yellow and it faded to a light yellow after 30 min. After the reaction was complete, the flask was cooled in a water bath and 8 ml of water and 8 ml of ether were added to it. The ethereal solution was washed three times with 8-ml portions of water, dried (MgS04), and concentrated. The products from 1 were determined by nmr analysis by integration of the signals for the methylene protons of 4 ( 3.55, m), the benzylic protons of 5 ( 4.15, s), and the benzylic protons of 1 ( 3.05, s). In several runs, the total recovery was determined by the use of octadecane or p-di-lert-butylbenzene as standards. The products from 2 were determined by nmr analysis by integration of the signals for the methyl protons of 2 ( 0.90, s), the methyl protons of 6 ( 1.22, s), and the methylene protons of 4 ( 3.55, m). In several cases, the total recovery was determined by the use of mesitylene as a standard. The products from 3 were determined by glpc analysis using benzophenone as a standard and correcting for thermal conductivity and extraction differences as previously described.ab Stability of Benzyl Phenyl Ketone (5) and Pivalophenone (6) to the Oxidation Conditions.-To 0.193 g (1.00 mmol) of 5 and 0.163 g (1.00 mmol) of 6 in 24 ml of acetonitrile and 7.4 ml of water at 80°was added 0.60 ml of a 1.00 M CAN solution.After 30 min at 80°, the mixture was cooled and 0.1822 g of standard (benzophenone) was added. Ether and water (20 ml of each) were added and after extraction the ether layer was separated, washed three times with water, dried (MgS04), and concentrated. Analysis by glpc (correcting for extraction and thermal conductivity differences) showed 97% recovery of 4 and quantitative recovery of 5.

Reactions of oxoosmium ligand complexes with nucleosides

“…Average molecular weight determinations suggest that essentially complete monomerization occurs in the concentration and pH range used for the kinetic studies. 13 Nikolskii et al21 report complete monomerization at much higher concentration in apparent contradiction to our results. 13 Transesterification Kinetics.…”

“…13 Nikolskii et al21 report complete monomerization at much higher concentration in apparent contradiction to our results. 13 Transesterification Kinetics. Quantitative measurements of the transesterification reaction were made using thymine and thymidine heterocyclic osmate esters11 as the osmium donor because of the convenience of following these components in the NMR spectrometer.…”

Identification of the cis-thymine glycol moiety in chemically oxidized and .gamma.-irradiated DNA by HPLC analysis

“…The large peak (fraction 42) represented the cis isomer which is known to be formed by KMn04 oxidation of the thymine moiety (Iida & Hayatsu, 1971; Frenkel et al, 1981). Isomerization of the cis (Barszcz et al, 1963;Subbaraman et al, 1973;Teoule et al, 1974) to a small amount of what probably is the trans glycol (fraction 40) occurred during the overnight incubation at 37 °C while the oxidized DNA was subjected to enzymatic digestion. There was no coincidence of 3H-containing material with [14C] thymine glycol, indicating that during the overnight enzymatic digestion there was no release of intact thymine glycol from the DNA backbone.…”

Tiaprofenic Acid-photosensitized Damage to Nucleic Acids: A Mechanistic Study Using Complementary in vitro Approaches

“…The pure isolated photoproducts were further characterized by 1 H and 13 C nuclear magnetic resonance and mass spectroscopic analysis (Table 1). Their assignment was based on comparison with the reported data (20)(21)(22)(23)(24)(25).…”