First synthesis of the antifungal oidiolactone C from trans-communic acid: cytotoxic and antimicrobial activity in podolactone-related compounds

J Org Chem. 2002 Apr 19;67(8):2501-8. doi: 10.1021/jo0161882.

Abstract

The synthesis of the fungicide oidiolactone C starting from diterpenic trans-communic acid was carried out with an overall yield of 11.7%. The key step in the process consists of a new bislactonization reaction catalyzed by Pd(II), which gives rise to the podolactone-type tetracyclic skeleton from a norlabdadienedioic acid. We also carried out a study of the structure-biological activity of different natural podolactones and their synthetic precursors. Thus, the highest cytotoxic activity was found in dienic dilactones with ether-type substitutions on C-17, whereas the closure of the gamma-lactone ring is not critical for presenting a maximal antimicrobial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / chemical synthesis*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Catalysis
  • Chromatography
  • Colonic Neoplasms
  • Diterpenes / chemistry*
  • Drug Screening Assays, Antitumor
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Juniperus / chemistry*
  • Leukemia P388
  • Lung Neoplasms
  • Magnetic Resonance Spectroscopy
  • Melanoma
  • Mice
  • Molecular Structure
  • Oxidation-Reduction
  • Plants, Medicinal / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Temperature
  • Tumor Cells, Cultured / drug effects

Substances

  • Antifungal Agents
  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Heterocyclic Compounds, 4 or More Rings
  • communic acid
  • oidiolactone C