325683-77-0Relevant academic research and scientific papers
Scalable Synthesis, in Vitro cccDNA Reduction, and in Vivo Antihepatitis B Virus Activity of a Phosphonomethoxydeoxythreosyl Adenine Prodrug
Luo, Min,Wu, Shuo,Kalkeri, Raj,Ptak, Roger G.,Zhou, Tianlun,Van Mellaert, Lieve,Wang, Chuanmin,Dumbre, Shrinivas G.,Block, Timothy,Groaz, Elisabetta,De Jonghe, Steven,Li, Yuhuan,Herdewijn, Piet
, p. 13851 - 13860 (2020/12/01)
Standard literature procedures for the chemical synthesis of l-threose nucleosides generally employ l-ascorbic acid as starting material. Herein, we have explored two alternative routes that start from either l-arabitol or l-diethyl tartrate, both affording 2-O-methyl-l-threofuranose as a key building block for nucleobase incorporation. The access to multigram quantities of this glycosyl donor in a reproducible fashion allows for the preparation of 2′-deoxy-α-l-threofuranosyl phosphonate nucleosides on a large scale. This methodology was applied to the gram scale synthesis of an aryloxy amidate prodrug of phosphonomethoxydeoxythreosyl adenine. This prodrug exerted potent activity against an entecavir-resistant hepatitis B virus (HBV) strain, while leading to a significant reduction in the levels of HBV covalently closed circular DNA in a cellular assay. Furthermore, its remarkable anti-HBV efficacy was also confirmed in vivo using a hydrodynamic injection-based HBV mouse model, without relevant toxicity and systemic exposure occurring.
Nonenzymatic oligomerization of RNA by TNA templates
Heuberger, Benjamin O.,Switzer, Christopher
, p. 5809 - 5811 (2007/10/03)
(Diagram presented) Cytosine TNA promotes nonenzymatic, template-directed oligomerization of complementary activated rGMP, leading to selective and efficient formation of RNA products. This process models "genetic takeover" of a pre-RNA by RNA.
The α-L-Threofuranosyl-(3′ → 2′)-oligonucleotide system ('TNA'): Synthesis and pairing properties
Schoening, Kai-Uwe,Scholz, Peter,Wu, Xiaolin,Guntha, Sreenivasulu,Delgado, Guillermo,Krishnamurthy, Ramanarayanan,Eschenmoser, Albert
, p. 4111 - 4153 (2007/10/03)
Our studies of α-L-Threofuranosyl-(3′ → 2′)-oligonucleotides ('TNA') are part of a systematic experimental inquiry into the base-pairing properties of potentially natural nucleic acid alternatives taken from RNA's close structural neighborhood. TNA is an efficient Watson-Crick base-pairing system and has the capability of informational cross-pairing with both RNA and DNA. This property, together with the system's constitutional and (presumed) generational simplicity, warrants special scrutiny of TNA in the context of the search for chemical clues to RNA's origin.
