Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation of Sarcophytonolides

J Org Chem. 2018 Sep 21;83(18):11028-11056. doi: 10.1021/acs.joc.8b01634. Epub 2018 Aug 23.

Abstract

Sarcophytonolides are cembranolide diterpenes isolated from the soft corals of genus Sarcophyton. Unified total synthesis of sarcophytonolides C, E, F, G, H, and J and isosarcophytonolide D was achieved. The synthetic routes feature NaHMDS- or SmI2-mediated fragment coupling, alkoxycarbonylallylation, macrolactonization, and transannular ring-closing metathesis. These total syntheses led to the absolute configurational confirmation of sarcophytonolide H, elucidation of sarcophytonolides C, E, F, and G, and revision of sarcophytonolide J and isosarcophytonolide D. We also evaluated the antifouling activity and toxicity of the synthetic sarcophytonolides H and J and their analogues as well as the cytotoxicity of the synthetic sarcophytonolides and the key synthetic intermediates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Chemistry Techniques, Synthetic
  • Diterpenes / chemical synthesis*
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • HL-60 Cells
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Diterpenes