Departments of Pharmaceutical Sciences, Chemistry, and Molecular Biology and Biochemistry, University of California , Irvine, California 92697-3958, United States.
J Org Chem. 2017 Jun 2;82(11):5910-5916. doi: 10.1021/acs.joc.7b00892. Epub 2017 May 19.
α-l-Threofuranosyl nucleic acid (TNA) is an artificial genetic polymer composed of vicinal 2',3'-phosphodiester bonds linking adjacent threofuranosyl nucleosides. TNA is one of a small number of genetic polymers that are both highly resistant to nuclease digestion and capable of cross-pairing with DNA and RNA. Although an efficient method for synthesizing TNA nucleosides has been reported, very few advances have been made in the synthesis of phosphorylated TNA compounds. Here, we describe a highly efficient method for synthesizing α-l-threofuranosyl nucleoside 3'-monophosphates (tNMPs), 3'-phosphoro(2-methyl)imidazolides (2-MeImptNs), and 3'-triphosphates (tNTPs) bearing the four genetic bases of adenine (A), cytosine (C), thymine (T), and guanine (G). We suggest that this strategy, which provides access to grams of tNMPs, hundreds of milligrams of 2-MeImptNs, and tens of milligrams of tNTPs, will help advance the use of TNA monomers in exobiology and biotechnology applications.
α-L-呋喃核糖核酸（TNA）是一种人工遗传聚合物，由相邻的呋喃核糖核苷之间的邻位 2'，3'-磷酸二酯键连接而成。TNA 是少数几种既能高度抵抗核酸酶消化，又能与 DNA 和 RNA 交叉配对的遗传聚合物之一。尽管已经报道了一种高效合成 TNA 核苷的方法，但在磷酸化 TNA 化合物的合成方面进展甚微。在这里，我们描述了一种高效合成带有腺嘌呤（A）、胞嘧啶（C）、胸腺嘧啶（T）和鸟嘌呤（G）四种遗传碱基的α-L-呋喃核糖核苷 3'-单磷酸酯（tNMP）、3'-磷酸（2-甲基）咪唑啉（2-MeImptN）和 3'-三磷酸酯（tNTP）的方法。我们建议，这种方法可以获得克级的 tNMP、数百毫克的 2-MeImptN 和数十毫克的 tNTP，这将有助于推进 TNA 单体在外生生物学和生物技术应用中的使用。
