Pyridine-stretched 2!-deoxyhypoxanthosine (strH) phosphoramidite was prepared in eight steps from Hoffer’s sugar (2!-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride). Improved synthesis of the Hoffer sugar was achieved without need for distillation or chromatographic separation of intermediates, or use of gaseous HCl. Conditions were optimised to provide a key nitrile intermediate for the preparation of strH whereby the cesium salt of 4(5)-nitroimidazole was glycosylated using Hoffer’s sugar. The nitrile intermediate was also used to prepare pyridine-stretched 2!-deoxyadenosine (strA) and pyridine-stretched 2!-deoxy-diaminopurine (strD). Preliminary studies indicate that strH forms a stronger, size-expanded base pair with adenine compared with the Watson-Crick thymine-adenine base pair.
Bibliographical note© The authors. Creative Commons License Deed; Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/
Funding: Scotia Pharmaceuticals; Royal Society; and EPSRC Mass Spectrometry Cenre for high-resolution mass spectra.
Copies of 1H and 13C NMR spectra are provided as supplementary material.
- Hoffer’s sugar
- pyridine-stretched purines
Clayton, R., Davis, M. L., Li, W., Fraser, W., & Ramsden, C. (2017). Preparation of pyridine-stretched 2’-deoxyhypoxanthosine phosphoramidite. Arkivoc, 2017(iii), 87-104. [OR-10075VP]. https://doi.org/10.3998/ark.5550190.p010.075