342-69-8Relevant articles and documents
Palladium-Catalyzed Thiomethylation via a Three-Component Cross-Coupling Strategy
Wang, Ming,Qiao, Zongjun,Zhao, Jiaoyan,Jiang, Xuefeng
supporting information, p. 6193 - 6197 (2018/09/25)
In this report, the combination of masked inorganic sulfur and dimethyl carbonate was designed to achieve thiomethylated cross coupling of aryl chlorides. Remarkably, this powerful strategy realized thiomethylation of nucleosides bearing unprotected ribose, chloride-containing pharmaceuticals with late-stage coupling, and herbicides possessing multiple heteroatoms and steric hindrance. Moreover, this protocol is practically amenable to multigram-scale synthesis with a lower catalysis loading and a higher yield.
High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
Bookser, Brett C.,Raffaele, Nicholas B.
, p. 173 - 179 (2007/10/03)
The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
Methylation of mercaptopurine, thioguanine, and their nucleotide metabolites by heterologously expressed human thiopurine S-methyltransferase
Krynetski, Eugene Y.,Krynetskaia, Natalia F.,Yanishevski, Yuri,Evans, William E.
, p. 1141 - 1147 (2007/10/03)
Thiopurine S-methyltransferase (TPMT), a cytosolic enzyme that exhibits genetic polymorphism, catalyzes S-methylation of mercaptopurine (MP) and thioguanine (TG), yielding S-methylated nucleobases that are inactive, whereas S-methylated nucleotides of these thiopurines are cytotoxic. A yeast- based heterologous expression system was therefore used to characterize human TPMT-catalyzed methylation of MP, TG, and their principal nucleotide metabolites [thioinosine monophosphate (TIMP) and thioguanosine monophosphate (TGMP), respectively]. MP, TG, TIMP, and TGMP were all substrates for human TPMT, exhibiting similar Michaelis-Menten kinetic parameters (K(m), 10.6- 27.1 μM; V(max), 31-59 nmol/min/mg of TPMT). Consistent with these kinetic parameters, human leukemia cells (CEM) incubated for 24 hr with 10 μM MP or TG accumulated significantly higher (2.3-fold, p = 0.01) concentrations of methyl-TIMP after MP incubation than methyl-TGMP after TG incubation, due to the 2.7-fold higher concentration of TIMP after MP incubation, compared with TG nucleotides (TGN) after TG incubation. Moreover, intracellular accumulation of TGN was 2.5-fold greater after TG incubation than after MP incubation (p = 0.01). These data establish that MP, TG, and their principal nucleotide metabolites are comparable substrates for polymorphic TPMT, and they demonstrate significant differences in the accumulation of active TGN and methylated nucleotides when leukemia cells are treated with MP versus TG.
