Abstract
Ipomoeassin F, a macrolide glycoresin containing an embedded disaccharide, possesses potent in vitro antitumor activity with an unknown mechanism of function. It inhibits tumor cell growth with single-digit nanomolar IC50 values, superior to many clinical chemotherapeutic drugs. To facilitate translation of its bioactivity into protein function for drug development, we report here a new synthesis for the gram-scale production of ipomoeassin F (3.8% over 17 linear steps) from commercially available starting materials. The conformation-controlled subtle reactivity differences of the hydroxyl groups in carbohydrates were utilized to quickly construct the disaccharide core, which, along with judicial selection of protecting groups, made the current synthesis very efficient. The same strategy was also applied to the smooth preparation of the 11R-epimer of ipomoeassin F for the first time. Cytotoxicity assays demonstrated the crucial role of the natural 11S configuration. In addition, cell cycle analyses and apoptosis assays on ipomoeassin F and/or its epimer were conducted. This work has laid a solid foundation for understanding the medicinal potential of the ipomoeassin family of glycolipids in the future.
References
Dec 16, 1983·Journal of Immunological Methods·T Mosmann
Mar 4, 1994·Carbohydrate Research·T M SlaghekJ F Vliegenthart
Feb 5, 1998·Cytometry·M van EngelandC P Reutelingsperger
Oct 31, 2003·Bioscience, Biotechnology, and Biochemistry·Masashi IshikawaTakeshi Kitahara
Apr 23, 2005·Journal of Natural Products·Shugeng CaoDavid G I Kingston
Jan 27, 2007·Journal of the American Chemical Society·Alois Fürstner, Takashi Nagano
Aug 8, 2007·Natural Product Research·Shugeng CaoDavid G I Kingston
May 8, 2008·The Journal of Organic Chemistry·David G I Kingston
Feb 21, 2009·Organic Letters·Maarten H D PostemaQunli Xu
Aug 22, 2009·Chemistry : a European Journal·Takashi NaganoAlois Fürstner
Mar 26, 2011·Current Medicinal Chemistry·P DeF Bedos-Belval
Jun 18, 2011·The Journal of Organic Chemistry·Ophélie MilhommeCyrille Grandjean
Oct 4, 2011·Carbohydrate Research·Guanghui ZongDaoquan Wang
Apr 17, 2012·Natural Product Reports·Malte GerschStephan A Sieber
Mar 19, 2014·Carbohydrate Research·Guanghui ZongDaoquan Wang
Jul 10, 2014·Chemical Reviews·Juan Xie, Nicolas Bogliotti
Citations
Feb 27, 2016·Organic Letters·Hui LiuJian-Song Sun
Mar 22, 2016·Organic Letters·Guanghui ZongWei Q Shi
Mar 8, 2018·Natural Product Reports·Jacob RodriguezMaciej A Walczak
Sep 1, 2017·Chemistry : a European Journal·Chaoqi LinJuan Xie
Sep 25, 2019·Chemistry, an Asian Journal·Shoji KobayashiAraki Masuyama
Apr 17, 2020·Organic & Biomolecular Chemistry·Jiuchang SunQian Wan
Feb 9, 2021·The Journal of Organic Chemistry·Stefanie MayrHendrik Zipse
Jan 13, 2021·Journal of Natural Products·David G I Kingston
Jan 2, 2018·European Journal of Medicinal Chemistry·Guanghui ZongWei Q Shi
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Surya B AdhikariGuijun Wang
Apr 11, 2017·The Journal of Organic Chemistry·Guanghui ZongWei Q Shi
Dec 3, 2020·The Journal of Organic Chemistry·Guanghui ZongWei Q Shi
May 7, 2019·Journal of the American Chemical Society·Guanghui ZongWei Q Shi
Sep 25, 2021·Journal of Cell Science·Pawel LeznickiStephen High
Oct 26, 2021·Chemistry : a European Journal·Stefanie Mayr, Hendrik Zipse
Jul 3, 2021·Communications Biology·Sarah O'KeefeStephen High