A New Approach for the Synthesis of Novel 5‐Substituted Isodeoxyuridine Analogs

Abstract

Cyclic sulfates of carbohydrates provide excellent synthons for the preparation of isodeoxyuridines through direct nucleophilic substitution reactions. These substitution reactions have exceptional regioselectivity. The products of the reactions served as key precursors for the synthesis of 5‐substituted isodeoxyuridines via the Stille and Heck coupling reactions. Interestingly, unprotected nucleosides could be used in these metal‐mediated functionalizations. The methodologies are general and allow ready access to a variety of C‐5 functionalized isomeric deoxyuridines, but also have the potential to be extended to other nucleoside analogs.

^†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

Keywords:

• Synthesis
• Functionalized isouridines
• Cyclic sulfate
• Cross‐coupling reactions

Acknowledgments

The project described was supported by Grant Number AI 32851 from the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Some aspects of this work were initiated at the University of Iowa prior to our move to the University of Georgia. We thank the Nebraska Center for Mass Spectrometry at the University of Nebraska‐Lincoln for the HRMS data.

Notes

^†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.