Synthesis of α-l-Threofuranosyl Nucleoside 3′-Monophosphates, 3′-Phosphoro(2-Methyl)imidazolides, and 3′-Triphosphates

5 years ago

Synthesis of α-l-Threofuranosyl Nucleoside 3′-Monophosphates, 3′-Phosphoro(2-Methyl)imidazolides, and 3′-Triphosphates

Saikat Bala, John C. Chaput, Jen-Yu Liao, Hui Mei

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.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b00892

DOI: 10.1021/acs.joc.7b00892