Thymidine -, reaction with

An isobutyl carbonate was prepared by reaction with isobutyl chloroformate (Pyr, 20°, 3 days, 73% yield), to protect the 5 -OH group in thymidine. It was cleaved by acidic hydrolysis (80% AcOH, reflux, 15 min, 88% yield). ... 

Interestingly, one-electron oxidants partly mimic the effects of OH radicals in their oxidizing reactions with the thymine moiety of nucleosides and DNA. In fact, the main reaction of OH radicals with 1 is addition at C-5 that yields reducing radicals in about 60% yield [34, 38]. The yield of OH radical addition at C-6 is 35% for thymidine (1) whereas the yield of hydrogen abstraction on the methyl group that leads to the formation of 5-methyl-(2 -de-oxyuridylyl) radical (9) is a minor process (5%). Thus, the two major differences in terms of product analysis between the oxidation of dThd by one-electron oxidants and that by the OH radical are the distribution of thymidine 5-hydroxy-6-hydroperoxide diastereomers and the overall percentage of methyl oxidation products. 

The Reformatsky type of reaction with Zn(0) was performed in situ and led to somewhat unstable phosphonodiamidite (step a) which was coupled with 5 -DMTr-thymidine to give the intermediate mononucleoside phospho-noamidite (step b). The latter was further coupled with 3 -acetyl-thymidine (step c). Couplings described in steps b and c were activated by tetrazole. The intermediate dinucleoside phosphonite was oxidized with (lS)-(+)-(10-camphorsulphonyl)oxaziridine (step d) or sulfurized with Beaucage reagent. The phosphonoamidites mentioned above were used in the solid-phase chemical synthesis of phosphonoacetate and thiophosphonoacetate oligonucleotides. 

Many DOHs, such as L-daunosamine, L-epivancosamine or L-ristosamine, contain an amino group at C3, which is introduced by an aminotransferase. The substrate for this reaction is the 3-keto sugar intermediate that arises as a consequence of the action of a 2,3-dehydratase. This transaminahon reaction has been biochemically characterized in the biosynthesis of L-epivancosamine [10]. Using a coupled reaction with EvaB (2,3-dehydratase) and EvaC (aminotransferase), with pyridoxal-5-phosphate (PEP) as a coenzyme and L-glutamate as a cosubstrate, they were able to show conversion of TDP-4-keto-2,6-dideoxyglucose into thymidine-5 -diphospho-3-amino-2,3,6-trideoxy-D-threo-hexopyranos-4-ulose. 

The 5,6-double bond in activated pyrimidines can participate in thermal [4-1-2] cyclization reactions as demonstrated by the 1,3-dipolar cycloaddition reactions of O-protected thymidine derivatives 483 with the nonstabilized azo-methine ylide 484, which is generated from trimethylamine AT-oxide by reaction with EDA <2002SC1977>. 

Oxidation of 5-substituted barbimric acids 258 with concomitant ring contraction has been shown to afford 2,4-oxazolidinediones 260 (Scheme 6.58). Similarly, examples of 5-aryl- and 5-heteroaryl-2,4-oxazolidinediones, for example, 231 and 233-240 (Table 6.8 and Fig. 6.19) have been prepared from alloxan hydrate 261. Thus, conversion of 261 to the dilauric acid intermediates 262 and reaction with sodium hydroxide gave the target compounds.Swiss chemists isolated 265 as a side product (12% yield) from the oxidation of the thymidine base in 263 during their preparation of 264 (Scheme 6.58). 

Synthesis of the thymidine derivative relies on the older two-step insertion of fluorine. Thus, the hydroxyl group in 3 -deoxythymidine benzoate (51-1) is first converted to the mesylate (51-2). Reaction with potassium fluoride in hydrogen fluoride replaces the mesylate by fluorine (51-3). The fact that this reaction, as that above, proceeds with retention of the configuration mles out simple displacement as the mechanism for this transform. The presence of the methyl group at position 5 negates the need for the chlorination step. Saponification then affords the antiviral agent alovudine (51-4) [52]. 

E)-5-(2-bromovinyl)-2 -deoxyuridine S -monophosphate <1> (<1>, IC50 0.0026 mM, reaction with thymidine, fusion protein with glutathione S-trans-ferase [5]) [5]... 

Conversion of the 3, 5 -diacetyl thymidine 652 (R = Me) to the chloro derivative 653 followed by reaction with sodium azide in anhydrous DMF gave 654, whose hydrolysis gave 655 (86JHC1401). The 2 -deoxy-2, 2 -difluoro analog of 655 was prepared (93EUP576230) (Scheme 132). 

Several cases of synthesis of a-D-galactosyl nucleotides from a-D-galactopyranosyl phosphate with bacterial enzymes have been reported. These included formation of UDP-Gal through reaction with uridine 5 -triphosphate22 or UDP-Glc,14,44 49 and of dTDP-Gal through interaction with thymidine 5 -triphosphate.50... 

Treatment of O-benzoyl anhydrothymidine 64 (R1 =Me R2 = COPh) with MgX2 (X = Br, I) in toluene at 100 °C afforded halo-substituted thymidines 65 (Nu = Br, I) in 70-75% yields <1995NN307, 1995TL873>. Alkylation of O-trityl anhydrothymidine with methyl triflate followed by reaction with NaBr or Nal gave the corresponding N(3)-methylated thymidines 65 (Nu = Br, I) in 70-90% yields <1993TL8411>. 

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