Bioactive rearranged and halogenated semisynthetic derivatives of the marine natural product sarcophine

J Nat Prod. 2004 Dec;67(12):2017-23. doi: 10.1021/np0497393.

Abstract

Cembranoids are natural diterpenes with 14-membered macrocyclic rings. The simplest natural cembranoid, (+)-cembrene, was isolated from pine oleoresin. Sarcophytols A and B are known cembranoids that inhibit tumor promotion. Sarcophine is a related cembranoid isolated from the Red Sea soft coral Sarcophyton glaucum. Sarcophine and its bioconversion products and semisynthetic derivatives are reported to possess cancer chemopreventive activity. Oxymercuration-demercuration of sarcophine using Hg(OAc)2 and NaBH4 afforded four new rearranged and hydroxylated products. Bromination of sarcophine with N-bromosuccinimide (NBS) furnished two new brominated and rearranged products. Reaction with iodine gave the known iso-sarcophinone and (+)-sarcophytoxin B. Structure elucidation was based on a combination of transition state modeling, molecular dynamics, mechanistic considerations, and 2D NMR data. The antiproliferative activity of the new products is also reported.

MeSH terms

  • 4-Butyrolactone* / analogs & derivatives*
  • 4-Butyrolactone* / chemical synthesis
  • 4-Butyrolactone* / chemistry
  • 4-Butyrolactone* / pharmacology
  • Animals
  • Anthozoa / chemistry*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Crystallography, X-Ray
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Hydrocarbons, Brominated / chemical synthesis*
  • Hydrocarbons, Brominated / chemistry
  • Hydrocarbons, Brominated / pharmacology
  • Indian Ocean
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Stereoisomerism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Diterpenes
  • Hydrocarbons, Brominated
  • cembrane
  • sarcophytol A
  • sarcophine
  • sarcophytol B
  • 4-Butyrolactone