An Improved One-Pot Synthesis of Nucleoside 5'-Triphosphate Analogues

被引：38

作者：

Gillerman, Irina ^{[1
]}

Fischer, Bilha ^{[1
]}

机构：

[1] Bar Ilan Univ, Dept Chem, Gonda Goldschmied Med Res Ctr, IL-52900 Ramat Gan, Israel

来源：

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2010年 / 29卷 / 03期

关键词：

Nucleoside 5'-triphosphate analogues; nucleoside 5'-triphosphorylation; Ludwig procedure; NUCLEOTIDE DERIVATIVES; 5'-TRIPHOSPHATES; TRIPHOSPHATES; DNA; PHOSPHORYLATION; POLYPHOSPHATES; 5'-PHOSPHATE; INHIBITION; PHOSPHATES; SUBSTRATE;

D O I：

10.1080/15257771003709569

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nucleoside 5'-triphosphate (NTP) analogues are valuable tools for biochemical and medicinal research. Therefore, a facile and efficient synthesis of NTP analogues is required. Here, we report on an improved nucleoside 5'-triphosphorylation procedure to obtain pure products after liquid chromotagrpahy (LC) separation with no need for high performance liquid chromatography (HPLC) purification. To improve the selectivity of the reaction we attempted the optimization of several parameters such as solvent, pyrophosphate nucleophilicity, time and temperature of the reaction. Eventually, the reaction was optimized by decreasing the temperature to -15 degrees C and increasing the reaction time to 2 hours, based on monitoring time-dependent product distribution using 31P NMR. Furthermore, the NTPs were obtained as pure products after LC separation, which was impossible in the original Ludwig procedure. Good yields were obtained for all studied natural and synthetic nucleosides.

引用

页码：245 / 256

页数：12

共 42 条

[31] CONVENIENT SYNTHESES OF CYTIDINE 5'-TRIPHOSPHATE, GUANOSINE 5'-TRIPHOSPHATE, AND URIDINE 5'-TRIPHOSPHATE AND THEIR USE IN THE PREPARATION OF UDP-GLUCOSE, UDP-GLUCURONIC ACID, AND GDP-MANNOSE
SIMON, ES
GRABOWSKI, S
WHITESIDES, GM
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (06) : 1834 - 1841
[32] NUCLEOSIDE 5'-PHOSPHORDIAMIDATES, SYNTHESIS AND SOME PROPERTIES
SIMONCSITS, A
TOMASZ, J
[J]. NUCLEIC ACIDS RESEARCH, 1975, 2 (07) : 1223 - 1233
[33] One-pot synthesis of nucleoside 5′-triphosphates from nucleoside 5′-H-phosphonates
Sun, Qi
Edathil, Jocelyn P.
Wu, Runzhi
Smidansky, Eric D.
Cameron, Craig E.
Peterson, Blake R.
[J]. ORGANIC LETTERS, 2008, 10 (09) : 1703 - 1706
[34] 2-CYANOETHYL PHOSPHATE AND ITS USE IN SYNTHESIS OF PHOSPHATE ESTERS
TENER, GM
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1961, 83 (01) : 159 - &
[35] CHEMICAL SYNTHESIS OF 5'-PYROPHOSPHATE AND TRIPHOSPHATE DERIVATIVES OF 3'-5' APA, APG, GPA AND GPG - CD STUDY OF EFFECT OF 5'-PHOSPHATE GROUPS ON CONFORMATION OF 3'-5' GPG
TOMASZ, J
SIMONCSITS, A
KAJTAR, M
KRUG, RM
SHATKIN, AJ
[J]. NUCLEIC ACIDS RESEARCH, 1978, 5 (08) : 2945 - 2957
[36] Synthetic nucleosides and nucleotides.: 40.: Selective inhibition of eukaryotic DNA polymeraseα by 9-(β-D-arabinofuranosyl)-2-(p-n-butylanilino)adenine 5′-triphosphate (BuAaraATP) and its 2′-up azido analog:: Synthesis and enzymatic evaluations
Tomikawa, A
Seno, M
Sato-Kiyotaki, K
Ohtsuki, C
Hirai, T
Yamaguchi, T
Kawaguchi, T
Yoshida, S
Saneyoshi, M
[J]. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 1998, 17 (1-3) : 487 - 501
[37] Vaghefi M., 2005, NUCLEOSIDE TRIPHOSPH, P408
[38] VANBOOM JH, 1975, TETRAHEDRON LETT, P2779
[39] A combination chemical and enzymatic approach for the preparation of azole carboxamide nucleoside triphosphate
Wu, WD
Bergstrom, DE
Davisson, VJ
[J]. JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (10) : 3860 - 3865
[40] YOSHIKAWA M, 1967, TETRAHEDRON LETT, P5065

← 1 2 3 4 5 →