Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors

Jun Tang1, *, Stacey A. Jones1, Jerry L. Jeffery1, Sonia R. Miranda1, Cristin M. Galardi1, David M. Irlbeck1, Kevin W. Brown1, Charlene B. McDanal1, Nianhe Han2, Daxin Gao2, Yongyong Wu2, Bin Shen2, Chunyu Liu2, Caiming Xi2, Heping Yang2, Rui Li2, Yajun Yu2, Yufei Sun2, Zhimin Jin2, Erjuan Wang2, Brian A. Johns1
1 GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA
2 ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China

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© Tang et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA; Tel: +1-919-483-4173; Fax: +1-919-315-6923; E-mail:


A macrocycle provides diverse functionality and stereochemical complexity in a conformationally preorganized ring structure, and it occupies a unique chemical space in drug discovery. However, the synthetic challenge to access this structural class is high and hinders the exploration of macrocycles. In this study, efficient synthetic routes to macrocyclized betulin derivatives have been established. The macrocycle containing compounds showed equal potency compared to bevirimat in multiple HIV-1 antiviral assays. The synthesis and biological evaluation of this novel series of HIV-1 maturation inhibitors will be discussed.

Keywords: Betulin derivative, HIV, macrocyclization, maturation inhibitor.