- Stereoselective N-glycosylation with N4-acyl cytosines and efficient synthesis of gemcitabine
-
Through systematical comparison of various N4-protected cytosine derivatives in the glycosylation step of gemcitabine synthesis, highly beta-stereoselective and high yielding TBAI catalyzed N-glycosylation was achieved with N4-Bz cytosine and anomeric mixture of 2,2‘-difluororibose mesylate donor. The subsequent global deprotection gave gemcitabine efficiently. Meanwhile, the anomeric chloride intermediate and fluoride-displaced side products of this N-glycosylation were identified, too. This new glycosylation method reveals the importance of N4-protection in the stereoselective preparation of pyrimidine nucleoside, also provides a potential alternative to current industrial process to gemcitabine.
- Liu, Tongchao,Tang, Jiadeng,Liang, Jianpeng,Chen, Yabin,Wang, Xiaowen,Shen, Jingkang,Zhao, Dongmei,Xiong, Bing,Cen, Jun-Da,Chen, Yue-Lei
-
p. 1203 - 1213
(2019/01/29)
-
- New cytosine derivatives as inhibitors of DNA methylation
-
DNA cytosine methylation catalyzed by DNA methyltransferase 1 (DNMT1) is an epigenetic method of gene expression regulation and development. Changes in methylation pattern lead to carcinogenesis. Inhibition of DNMT1 activity could be a good strategy of safe and efficient epigenetic therapy. In this work, we present a novel group of cytosine analogs as inhibitors of DNA methylation. We show new methods of synthesis and their effect on in vitro reaction of DNA methylation. Almost all of analyzed compounds inhibit DNA methyltransferase activity in the competitive manner. Ki values for the most potent compound 4-N-furfuryl-5,6-dihydroazacytosines is 0.7 μM. These compounds cause also a decrease of 5-methylcytosine (m5C) level in DNA of mammalian HeLa and HEK293 cells.
- Plitta, Beata,Adamska, Ewelina,Giel-Pietraszuk, Malgorzata,Fedoruk-Wyszomirska, Agnieszka,Naskret-Barciszewska, Miroslawa,Markiewicz, Wojciech T.,Barciszewski, Jan
-
p. 243 - 254,12
(2020/07/30)
-
- CYTOSINE ANALOGUE, A METHOD OF PREPARATION OF A CYTOSINE ANALOGUE, A DNA METHYLTRANSFERASE 1 INHIBITOR, A METHOD FOR DNA METHYLATION INHIBITION, THE USE OF THE ANALOGUE IN THE TREATMENT OF DISEASES ASSOCIATED WITH DEVIATIONS FROM NORMAL DNA METHYLATION
-
This invention provides a cytosine analogue, a method of preparation of a cytosine analogue, a DNA rhethyltransferase 1 inhibitor, a method for DNA methylation inhibition, the use of the analogue in the treatment of diseases associated with deviations from normal DNA methylation. More precisely, the invention relates to various derivatives of cytosine, as well as methods of preparation of mono- and multi-1,4,5 and 6-substituted cytosines. In general, the solution relates to providing effective modulators of DNA methylation which could be used in prevention and treatment of diseases associated with DNA methylation level disorders.
- -
-
Page/Page column 4; 8
(2013/02/27)
-
- A CYTOSINE ANALOGUE, A METHOD OF PREPARATION OF A CYTOSINE ANALOGUE, A DNA METHYLTRANSFERASE 1 INHIBITOR, A METHOD FOR DNA METHYLATION INHIBITION, THE USE OF THE ANALOGUE IN THE TREATMENT OF DISEASES ASSOCIATED WITH DEVIATIONS FROM NORMAL DNA METHYLATION
-
This invention provides a cytosine analogue, a method of preparation of a cytosine analogue, a DNA rhethyltransferase 1 inhibitor, a method for DNA methylation inhibition, the use of the analogue in the treatment of diseases associated with deviations from normal DNA methylation. More precisely, the invention relates to various derivatives of cytosine, as well as methods of preparation of mono- and multi- 1,4,5 and 6-substituted cytosines. In general, the solution relates to providing effective modulators of DNA methylation which could be used in prevention and treatment of diseases associated with DNA methylation level disorders.
- -
-
Page/Page column 8-9; 17
(2011/10/10)
-
- Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
-
A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases, including 2,6-diaminopurine, attached to a polyamide backbone, and contain alkyl amine side chains.
- -
-
-
- Peptide nucleic acids having 2,6-diaminopurine nucleobases
-
A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. The peptide nucleic acids of the invention comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone. Some PNAs of the invention also contain C1-C8alkylamine side chains.
- -
-
-
- Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
-
A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, and contain C1 -C8 alkylamine side chains. Methods of enhancing the solubility, binding affinity and sequence specificity of PNAs are provided.
- -
-
-
- Peptide nucleic acids having amino acid side chains
-
A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, and contain alkylamine side chains.
- -
-
-
- Mechanism of formation of N2-benzylguanine in the reaction of 2-amino- 6-chloropurine with sodium benzyl oxide, and benzylation of nucleic acid bases
-
The mechanism of formation of N2-benzylguanine in the reaction of 2- amino-6-chloropurine with a large excess (12-13 molar eq) of sodium benzyl oxide in benzyl alcohol at 130°C was studied. N2,O6-Dibenzylguanine, a reaction intermediate, was isolated and a possible mechanism for its formation is discussed. Furthermore, using this sodium benzyl oxide system, benzylation at the amino group of nucleic acid bases was facilitated.
- Koyama, Ken-Ichi,Hitomi, Kenichi,Terashima, Isamu,Kohda, Kohfuku
-
p. 1395 - 1399
(2007/10/03)
-