The cephalostatins. 21. Synthesis of bis-steroidal pyrazine rhamnosides (1)

J Nat Prod. 2011 Sep 23;74(9):1922-30. doi: 10.1021/np200411p. Epub 2011 Sep 7.

Abstract

The synthesis of bis-steroidal pyrazines derived from 3-oxo-11,21-dihydroxypregna-4,17(20)-diene (4) and glycosylation of a D-ring side chain with α-L-rhamnose have been summarized. Rearrangement of steroidal pyrazine 10 to 14 was found to occur with boron triflouride etherate. Glycosylation of pyrazine 10 using 2,3,4-tri-O-acetyl-α-L-rhamnose iodide led to 1,2-orthoester-α-L-rhamnose pyrazine 17b. By use of a persilylated α-L-rhamnose iodide as donor, formation of the orthoester was avoided. Bis-steroidal pyrazine 10 and rhamnosides 17b and 21c were found to significantly inhibit cancer cell growth in a murine and human cancer cell line panel. Pyrazine 9 inhibited growth of the nosocomial pathogen Enterococcus faecalis.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Boranes / chemistry
  • Cardiac Glycosides / chemical synthesis*
  • Cardiac Glycosides / chemistry
  • Cardiac Glycosides / pharmacology
  • Enterococcus faecalis / drug effects*
  • Glycosylation
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Phenazines / chemistry*
  • Pyrazines / chemical synthesis*
  • Pyrazines / chemistry
  • Pyrazines / pharmacology
  • Rhamnose / analogs & derivatives
  • Rhamnose / chemical synthesis*
  • Rhamnose / chemistry
  • Rhamnose / pharmacology
  • Spiro Compounds / chemistry*
  • Steroids / chemical synthesis*
  • Steroids / chemistry
  • Steroids / pharmacology

Substances

  • Antineoplastic Agents
  • Boranes
  • Cardiac Glycosides
  • Phenazines
  • Pyrazines
  • Spiro Compounds
  • Steroids
  • cephalostatin I
  • boron trifluoride etherate
  • Rhamnose