10.1016/j.tet.2007.06.040
The research focuses on the development of a novel nucleoside analogue, specifically 20-deoxy-trans-3',4'-bridged nucleic acids (trans-3',4'-BNA), which feature an S-type sugar conformation. The purpose of this study was to synthesize two new trans-3',4'-BNA monomers from thymidine, with the aim of creating stable duplexes or triplesxes with single- or double-stranded nucleic acids. The research concluded that these novel nucleosides, with their typical S-type sugar conformation, meet the conformational requirements of the B-type DNA duplex, making them strong candidates for ideal DNA structure mimics. The chemicals used in the synthesis process included thymidine, osmium tetroxide, benzyl chloromethyl ether (BOMCl), dibutyltindimethoxide, chloromethyl methyl ether (MOMCl), and various other reagents employed in the protection and deprotection steps, oxidation, reduction, and construction of the trans-fused ring structures. The synthesized nucleosides were confirmed by X-ray crystallography, which indicated their furanose rings had a typical S-type conformation, similar to that observed in the B-type helical structure of the DNA duplex.
10.1039/c1ob05247k
The research aims to develop a facile synthesis method for hydroxymethylcytosine (hmC)-containing oligonucleotides (ODNs) and investigate their reactivity upon osmium oxidation. The study synthesizes hmC-containing ODNs using a straightforward route starting from thymidine and involving protection, bromination, and amination steps, ultimately converting the nucleoside into phosphoramidite form for DNA autosynthesizer use. The synthesized ODNs form stable duplexes with complementary DNA, exhibiting similar melting temperatures and enzymatic digestion properties to methylated counterparts. Osmium oxidation, a method previously used for detecting 5-methylcytosine (mC), is tested on hmC-containing ODNs under specific reaction conditions, revealing that hmC is oxidized as efficiently as mC, forming a stable ternary complex. The study concludes that osmium oxidation is a viable method for detecting hmC in DNA, potentially advancing epigenetic studies. Key chemicals used include thymidine, acetic anhydride, N-bromosuccinimide, 3-hydroxypropionitrile, phosphorus oxychloride, ammonia, di(n-butyl)formamidine, potassium osmate, potassium hexacyanoferrate(III), and bipyridine.
10.1016/j.tet.2005.07.089
The study focuses on the synthesis and conformational analysis of amide-linked cyclic homooligomers of a thymidine-based nucleoside amino acid. These cyclic molecules were synthesized using a BOP reagent in the presence of DIPEA under dilute conditions, starting from a linear dimer of a thymidine-based nucleoside amino acid. The chemicals used in the synthesis process include BOP reagent, DIPEA, DMF, H2, Pd-C, and various protecting groups like Boc and BOM, which are common in peptide synthesis to protect functional groups during the assembly process. The purpose of these chemicals is to facilitate the formation of the cyclic structures and to protect and deprotect specific functional groups during the synthesis, allowing for the controlled assembly of the complex cyclic molecules. The study also involved NMR and constrained MD studies to analyze the conformational structures of the synthesized cyclic products, revealing that they had symmetrical structures with NH and CO groups oriented nearly perpendicular to the plane of the macrocyclic ring.
10.1021/jm00156a025
The research focused on the synthesis and evaluation of fourteen derivatives of thymidine, which were substituted at the 5'-position with various reactive groups, as potential inhibitors of enzymes involved in purine and pyrimidine nucleoside metabolism. The purpose was to investigate their cytotoxicity against H.Ep.-2 and L1210 cells in culture and their activity against P388 leukemia in mice. The study found that compounds 2, 3, and 7 were cytotoxic to the cultured cells, and compounds 2 and 3 showed good activity against P388 leukemia. The most active compound, 5'-(bromoacetamido)-5'-deoxythymidine (2), demonstrated a 71% increase in life span (ILS) in the P388 mouse leukemia screen and was identified as an irreversible inhibitor of thymidylate synthase. The chemicals used in this process included haloacetamido, bromo- and chloro-N-methylacetamido, bromomethanesulfonamido, ethyloxamido, (fluorosulfonyl)benzamido, and (phenoxycarbonyl)amino groups, among others, to synthesize the derivatives. The study concluded that while there was no close correlation between chemical reactivity and biological activity, the biologically active compounds had half-lives ranging from less than 30 seconds to 6 minutes, with the most active compound having a half-life of 6 minutes.
10.1016/S0040-4039(00)89270-9
The research focuses on the one-step protection of the nucleoside ease in thymidine and uridine. The purpose of this study was to address the issue of unwanted side reactions that occur during the synthesis of oligonucleotides via the phosphotriester approach, particularly on the imide moieties of guanine, uracil, and thymine. The researchers aimed to protect these vulnerable positions by introducing a protecting group that could be selectively attached and later removed without causing damage to the nucleosides. The study concluded that 4-nitrophenylsulfonylethene (1) could be used for the selective protection of O' in the uracil or thymine residue in the corresponding unprotected nucleosides. The protecting group, 4-nitrophenylsulfonylethyl, was stable under various conditions but could be cleaved within 2.5 hours at 50-55°C by concentrated aqueous ammonia via β-elimination. Key chemicals used in this process included 4-nitrophenylsulfonyl ethene (1), thymidine (3), uridine (5), and tetrabutylammonium hydroxide as a catalyst. The researchers also used Dowex cation exchanger (H+-cycle) for purification and triethylamine for β-elimination. The protection and deprotection processes were confirmed through infrared spectra analysis and synthesis of the compounds via an alternative method, which yielded identical results.
10.1039/c39890000997
T. Sudhakar Rao and Colin B. Reese describe a new method for synthesizing 2,3'-anhydrothymidine (3), a key intermediate in the production of the antiretroviral drug 3'-azido-3'-deoxythymidine (AZT). The authors discovered that heating thymidine (2) with an excess of diphenyl sulphite in dimethylacetamide solution in the presence of a catalytic amount of 1-methylimidazole at 156°C for 45 minutes yields 2,3'-anhydrothymidine (3) in approximately 65% yield. This method is advantageous over previous procedures, such as the use of 2-chloro-1-diethylamino-1,1,2-trifluoroethane, due to the greater accessibility of diphenyl sulphite. The synthesized 2,3'-anhydrothymidine (3) can then be converted into AZT by reacting with lithium azide, achieving a 71% yield of AZT. This streamlined synthesis offers a more efficient route for the production of AZT, which is crucial for the treatment of AIDS patients.
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