Synthesis of a novel C-nucleoside prodrug for treatment of Hepatitis B Open Access

Wan, Anqi (Spring 2020)

Permanent URL:


In an effort to treat newly emerging HBV viral strains effectively, there is a need to develop novel nucleoside analogs with improved biological properties. Nucleot(s)ide based anti- HBV agents suppress the HBV viral replication by inhibiting the key polymerase activity known as reverse transcriptase. C-nucleosides offer a more stable alternative to the conventional nucleoside analogs, due to their stable C-C linkage in place of common C-N glycosidic bond. We designed a novel C-nucleoside analog and its phosphoramidate prodrug for targeting HBV and the prodrug was synthesized successfully in 10 steps with overall yield of 2.84%.

Table of Contents

Introduction 1

Figure 1. Life cycle of HBV 2

Figure 2. Phosphorylation of nucleoside analogs 3

Figure 3. Structures of current nucleoside analogues to HBV infection 5

Figure 4. N-nucleoside and C-nucleoside 6

Figure 5. Structure of GS-6620 6

Figure 6. Novel C-nucleoside and its prodrug 7

Results and discussion 8

Scheme 1. Attempted synthesis 8

Scheme 2. Synthesis of protected lactol 9

Scheme 3. Oxidation of lactol to lactone 10

Scheme 4. Coupling of lactone to nucleobase 11

Scheme 5. Synthesis of C-Nucleoside 12

Scheme 6. Synthesis of phosphoramidate prodrug (Method 1) 13

Scheme 7. Synthesis of phosphoramidate prodrug (Method 2) 13

Experimental 14

References 25 

About this Honors Thesis

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
  • English
Research Field
Committee Chair / Thesis Advisor
Committee Members
Last modified

Primary PDF

Supplemental Files