Total synthesis, revised structure, and biological evaluation of biyouyanagin A and analogues thereof

J Am Chem Soc. 2008 Aug 20;130(33):11114-21. doi: 10.1021/ja802805c. Epub 2008 Jul 23.

Abstract

Isolated from Hypericum species H. chinese L. var. salicifolium, biyouyanagin A was assigned structure 1a or 1b on the basis of NMR spectroscopic analysis. This novel natural product exhibited significant anti-HIV properties and inhibition of lipopolysaccharide-induced cytokine production. Described herein are the total syntheses of biyouyanagin A and several analogues (3-11), structural revision of biyouyanagin A to 2b, and the biological properties of all synthesized compounds. The total synthesis proceeded through cascade sequences that efficiently produced enantiomerically pure key building blocks 15b (ent-zingiberene) and 18 (hyperolactone C) and featured a novel [2 + 2] photoinduced cycloaddition reaction which occurred with complete regio- and stereoselectivity. Biological investigations with the synthesized biyouyangagins A (2-11) and hyperolactones C (12-16) revealed that the activity of biyouyanagin A most likely resides in its hyperolactone C structural domain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Cytokines / biosynthesis
  • Cytokines / drug effects
  • Drug Evaluation, Preclinical
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology
  • HIV / drug effects
  • Humans
  • Hypericum / chemistry
  • Inhibitory Concentration 50
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Lymphocytes / drug effects
  • Magnetic Resonance Spectroscopy / methods
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Sensitivity and Specificity
  • Sesquiterpenes / chemical synthesis*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology
  • Spiro Compounds
  • Stereoisomerism

Substances

  • Anti-HIV Agents
  • Cytokines
  • Furans
  • Lipopolysaccharides
  • Sesquiterpenes
  • Spiro Compounds
  • biyouyanagin A
  • hyperolactone C