149666-71-7Relevant academic research and scientific papers
An improved synthesis of 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) and the fate of the precursor, 2,3'-anhydro-5'-O-(4,4'-dimethoxytrityl)-thymidine
Cleij, M. C.,Steel, C. J.,Brady, F.,Ell, P. J.,Pike, V. W.,Luthra, S. K.
, p. S871 - S873 (2001)
The fate of the precursor, 2,3'-anhydro-5'-O-(4,4'-dimethoxytrityl)-thymidine was investigated during the synthesis of [18F]FLT with the aim of improving the radiochemical yield. This precursor was shown to undergo a rapid base catalysed elimination reaction and to be consumed within 5-10 min. The by-product was identified. Modification of the syntheis has produced between 1.85-3.70 GBq (50-199 mCi) of [18F]FLT in 60 min using an automated synthesis system.
Probing the binding requirements of modified nucleosides with the dna nuclease snm1a
Dürr, Eva-Maria,McGouran, Joanna F.
, (2021/06/21)
SNM1A is a nuclease that is implicated in DNA interstrand crosslink repair and, as such, its inhibition is of interest for overcoming resistance to chemotherapeutic crosslinking agents. However, the number and identity of the metal ion(s) in the active site of SNM1A are still unconfirmed, and only a limited number of inhibitors have been reported to date. Herein, we report the synthesis and evaluation of a family of malonate-based modified nucleosides to investigate the optimal positioning of metal-binding groups in nucleoside-derived inhibitors for SNM1A. These compounds include ester, carboxylate and hydroxamic acid malonate derivatives which were installed in the 5′-position or 3′-position of thymidine or as a linkage between two nucleosides. Evaluation as inhibitors of recombinant SNM1A showed that nine of the twelve compounds tested had an inhibitory effect at 1 mM concentration. The most potent compound contains a hydroxamic acid malonate group at the 5′-position. Overall, our studies advance the understanding of requirements for nucleoside-derived inhibitors for SNM1A and indicate that groups containing a negatively charged group in close proximity to a metal chelator, such as hydroxamic acid malonates, are promising structures in the design of inhibitors.
New telluride-mediated elimination for novel synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides
Sheng, Jia,Hassan, Abdalla E. A.,Huang, Zhen
, p. 3725 - 3729 (2008/09/20)
(Chemical Equation Presented) Several 2′,3′-dideoxynucleosides (ddNs) and 2′,3′-didehydro-2′,3′-dideoxynucleosides (d4Ns) are FDA-approved anti-HIV drugs. Via conveniently synthesized 2,2′-anhydronucleosides, we have developed a novel synthesis of d4Ns by discovering and applying a new telluride-mediated elimination reaction. Our experiment results show that after substitution of 2,2′-anhydronucleosides with a telluride monoanion, a telluride intermediate is formed, and its elimination leads to formation of the olefin products (d4Ns). Our mechanistic study indicates that this telluride-assisted reaction consists of two steps: substitution (or addition) and elimination. By using dimethyl ditelluride (0.1 equiv) as the reagent, d4Ns can be synthesized with yields up to 90% via this telluride-mediated elimination. Our novel strategy has great potential to simplify synthesis of these drugs and to further reduce cost of AIDS treatment and will also facilitate development of novel d4N and ddN analogues.
