Abstract

Seven metabolites of 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine (WS070117) were synthesized by deacetylation, hydrolysis, cyclization, sulfonylation and glycosylation reactions, respectively. All these compounds, which could be useful as material standards for metabolic research, were characterized by NMR and HPLC-MS (ESI) analyses.

Highlights

  • Introduction21 ,31 ,51 -Tri-O-acetyl-N6 -(3-hydroxyphenyl) adenosine ( known as WS070117) is a new adenosine analog anti-hyperlipidemic drug candidate currently in many preclinical studies [1,2,3,4,5]

  • State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China; Abstract: Seven metabolites of 21,31,51 -tri-O-acetyl-N6 -(3-hydroxyphenyl) adenosine (WS070117)

  • Seven metabolites of WS070117 were observed in the HPLC trace

Read more

Summary

Introduction

21 ,31 ,51 -Tri-O-acetyl-N6 -(3-hydroxyphenyl) adenosine ( known as WS070117) is a new adenosine analog anti-hyperlipidemic drug candidate currently in many preclinical studies [1,2,3,4,5]. Guo and coworkers have investigated and elucidated the in vivo metabolites of WS070117 in rat urine after oral administration of WS070117 by HPLC-DAD, ESI-MS and Off-Line Microprobe NMR [6]. Seven metabolites of WS070117 were observed in the HPLC trace (the metabolites are ranked M2–M8 according to the retention time; Figure 1). The structure elucidation results unambiguously revealed that there are two phase I metabolites, including a deacetylation product of WS070117 (M8) and an adenine derivative formed by the loss of ribofuranose (M7). There are five phase II metabolites: M6 is the oxidation product of M7 at C-8; M2 and M4 are the glycosylation products of M7 and M8 on the phenolic hydroxyl groups, respectively; M3 and M5 are the sulfonylation products of M6 and M8, respectively. The synthesis of the above metabolites was carried out to provide metabolites material standards for preclinical pharmacokinetic studies

Results and Discussion
The structuresof ofthe the WS070117
General
Synthesis of Intermediate 7
Conclusions
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call