Erythrolic acids A-E, meroterpenoids from a marine-derived Erythrobacter sp

J Org Chem. 2012 Apr 6;77(7):3401-7. doi: 10.1021/jo300197z. Epub 2012 Mar 12.

Abstract

Erythrolic acids A-E (1-5) are five unusual meroterpenoids isolated from the bacterium Erythrobacter sp. derived from a marine sediment sample collected in Galveston, TX. The structures were elucidated by means of detailed spectroscopic analysis and chemical derivatization. The erythrolic acids contain a 4-hydroxybenzoic acid appended with a modified terpene side chain. The side-chain modifications include oxidation of a terminal methyl substituent and in the case of 1-4 addition of a two-carbon unit to give terpene side chains of unusual length: C22 for 1 and 2, C17 for 3, and C12 for 4. The relative and absolute configurations of the meroterpenoids were determined by coupling constant, NOE, and Mosher's analysis. In vitro cytotoxicity toward a number of nonsmall cell lung cancer (NSCLC) cell lines revealed only modest activity for erythrolic acid D (4) (2.5 μM against HCC44). The discovery of these unusual diterpenes, along with the previously reported erythrazoles, demonstrates the natural product potential of a previously unstudied group of bacteria for drug discovery. The unusual nature of the terpene side chain, we believe, involves an oxidation of a terminal methyl group to a carboxylic acid and subsequent Claisen condensation with acetyl-CoA.

Publication types

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

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / chemistry*
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Parabens / chemistry*
  • Sphingomonadaceae / chemistry*
  • Terpenes / chemistry*

Substances

  • Parabens
  • Terpenes
  • 4-hydroxybenzoic acid