65358-18-1Relevant articles and documents
Synthetic Approaches for the Preparation of Phosphoramidate Prodrugs of 2′-Deoxypseudoisocytidine
Serpi, Michaela,De Biasi, Roberto,Pertusati, Fabrizio,Slusarczyk, Magdalena,McGuigan, Christopher
, p. 424 - 436 (2017)
A synthetic procedure for the preparation of phosphoramidate prodrugs of C-nucleosides is reported. Different phosphorochloridates were reacted with 3′-O-protected N-acetyl-2′-deoxypseudoisocytidine or 3′-O-protected 2′-deoxypseudoisocytidine, followed by acidic hydrolysis of the protecting group. In the presence of the N-acetyl moiety, the enolisable keto group of the nucleobase was able to react (like the 5′-OH) with the phosphorochloridates to give bisphosphorylated derivatives. Epimerisation (β to α) occurred if the amino group of the nucleobase was unprotected. These side reactions demonstrate the peculiar behaviour of C-nucleosides compared to their nucleoside analogues. It was demonstrated that the first enzymatic activation step for this new class of prodrugs can be mediated by carboxypeptidase and that it follows the same pathway and rate reported for ProTides of more conventional nucleoside analogues. These new phosphoramidate derivatives deserve further investigation for their therapeutic potential as anti-cancer agents.
Nucleosides. 121. Improved and General Synthesis of 2'-Deoxy C-Nucleosides. Synthesis of 5-(2-Deoxy-β-D-erythro-pentofuranosyl)uracil, -1-methyluracil, -1,3-dimethyluracil, and -isocytosine
Pankiewicz, Krzysztof,Matsuda, Akira,Watanabe, Kyoichi A.
, p. 485 - 488 (2007/10/02)
5-(2-Deoxy-β-D-erythro-pentofuranosyl)-1,3-dimethyluracil (6a), -1-methyluracil (6b), -uracil (6c), and -isocytosine (6d) were synthesized.Compounds 6b-d are C-nucleoside isosteres of thymidine, 2'-deoxyuridine, and 2'-deoxycytidine, respectively. 1,3-Dimethylpseudouridine (1a), 1-methylpseudouridine (1b), pseudouridine (1c), and pseudoisocytidine (1d) were treated with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in pyridine to afford the corresponding 3',5'-tetraisopropyldisiloxanyl derivatives 2 which were converted into the respective 2'-O- C-nucleosides 3.Compounds 3a,b were converted directly into the corresponding 2'-deoxy β-C-nuleosides 5a,b exclusively by reduction with n-Bu3SnH.For the synthesis of 2'-deoxy β-C-nucleosides 5c,d, the intermediates 3c,d were trimethylsilylated prior to n-Bu3SnH treatment.Deprotection of 5a-d was effected by treatment with n-Bu4NF, and the corresponding free 2'-deoxy β-C-nucleosides 6a-d were obtained in good yields.
Pyrimidine to pyrimidine transformation process
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, (2008/06/13)
There is provided a novel process for pyrimidine to pyrimidine transformations by the displacement of the 1,2,3-portion of a pyrimidine by a 1,3-ambident nucleophile. The novel process requires that the 1 and 3 nitrogens of the pyrimidine moiety be substituted. The novel process makes available, inter alia, novel uracils, simple methods of radioisotopically labeling pyrimidine nuclei, a simple and inexpensive method of preparing the important antiviral and antileukemic material pseudoisocytidine and its new active analog 2'-deoxypseudoisocytidine.
