5'-O-Tritylthymidine

Synthesized in the following manner according to literature [Nucleosides Nucleotides, 8, 1529-1535 (1989)]: In a stream of nitrogen, triphenylmethyl chloride (15 g, 53.7 mmols) was added to a pyridine (40 ml) solution of thymidine (10 g, 41.3 mmols) at room temperature, and the mixture was stirred for 21.5 hours at room temperature. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the system was extracted with a methylene chloride solution. The organic layer was washed with a saturated aqueous solution of sodium chloride, and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (ethyl acetate:n-hexane = 1:1)* to obtain Compound 41 (19.4 g, 97.1percent) as a colorless acicular substance.In a 25ml round bottom flask 100mg (0.39mmol) of4was evaporated 3 times with 3mL of dry pyridine and dissolved in 3mL of dry pyridine. Trityl chloride (120.0mg, 0.43mmol) was added and the reaction mixture was heated at 65°C for 16h under argon atmosphere. After 16h, the mixture was cooled to room temperature, quenched with 3mL of MeOH and stirred for 30min. The mixture was evaporated to dryness. The obtained crude compound was purified by column chromatography to obtain 92mg (48percent) of17. TLC (CHTo a previously cooled (0-5° C.) mixture of 2, 2'-anhydro-1-(5-O-trityl--D-arabinofuranosyl)thymine 4 (241 mg, 0.5 mmol) and 15-crown-5 (0.15 mL, 0.75 mmol) in anhydrous THF (10 mL) was added Red-Al (65percent wt. in toluene, 0.23 mL, 0.75 mmol) dropwise over a period of 5 minutes. The mixture was maintained at 0-5° C. under argon. The reaction was monitored by t.l.c. (silica, 5:95 methanol in dichloromethane) and HPLC analysis. After stirring at 0-5° C. for 1 hour, an aliquot from reaction mixture was taken into HPLC grade THF (ca. 1 mL), quenched with drops of distilled water and injected on an HPLC instrument. The result indicated only 8percent AUC (area under curve) of starting material remained and 70.8percent of product was present. The reaction was quenched by adding saturated aqueous NH2, 2'-Anhydro-1-(5-O-trityl--D-arabinofuranosyl) thymine (Q (4.30 g, 8.91 mmol) was suspended in anhydrous tetrahydrofuran (43 mL) and cooled to about 0-5° C. using an ice-bath. In a separate flask immersed in an ice-bath at about 0-5° C., a 65percent wt solution of Red-Al in toluene (3.26 mL, 10.69 mmol) was diluted by addition to anhydrous tetrahydrofuran (21.5 mL). This diluted Red-Al solution was cooled to about 0-5° C. and added dropwise via syringe to the suspension of 2, 2'-anhydro-1-(5-O-trityl--D-arabinofuranosyl) thymine (2) in tetrahydrofuran. The rate of dropwise addition of the Red-Al solution is critical to the reaction and was completed in about 1 hour. The resulting clear solution was maintained at about 0-5° C. for 1 hour after which time, t.l.c. analysis (10percent methanol in dichloromethane) indicated the presence of starting material (R

5'-O-Tritylthymidine is an inhibitor of TK-2 and inhibits angiogenesis[1]. 5'-O-Tritylthymidine targets FAK-Mdm-2 interactions, decreasing cell viability and increasing apoptosis.

Molecular Weight:484.5
XLogP3:3.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:7
Exact Mass:484.19982200
Monoisotopic Mass:484.19982200
Topological Polar Surface Area:88.1
Heavy Atom Count:36
Complexity:765
Undefined Atom Stereocenter Count:3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes