Semisynthesis and biological activity of stemofoline alkaloids

J Nat Prod. 2009 Apr;72(4):679-84. doi: 10.1021/np800806b.

Abstract

The semisynthesis of the Stemona alkaloids (3'R)-stemofolenol (1), (3'S)-stemofolenol (2), methylstemofoline (3), and (3'S)-hydroxystemofoline (5) and the unnatural analogues (11E)-methylstemofoline (15) and 3'R-hydroxystemofoline (11) has been achieved starting from (11Z)-1',2'-didehydrostemofoline (4). This synthesis allowed, for the first time, access to diastereomerically enriched samples of 1 and 2 and the assignment of their absolute configurations at C-3'. These compounds were obtained in sufficient quantities to allow for their biological testing. In a quantitative assay as AChE inhibitors, (11Z)-1',2'-didehydrostemofoline (4) and (3'S)-hydroxystemofoline (5) were found to be the most active.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Candida albicans / drug effects
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Escherichia coli / drug effects
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Stemonaceae / chemistry*
  • Stereoisomerism

Substances

  • (11Z)-1',2'-didehydrostemofoline
  • (3'S)-hydroxystemofoline
  • Alkaloids
  • Cholinesterase Inhibitors
  • Heterocyclic Compounds, 4 or More Rings
  • didehydrostemofoline
  • stemofoline