Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Total synthesis and evaluation of phostriecin and key structural analogues

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Burke, C. P.
  • Swingle, M. R.
  • Honkanen, R. E.
  • Boger, Dale

publication date

  • November 2010

journal

  • Journal of Organic Chemistry  Journal

abstract

  • Full details of the total synthesis of phostriecin (2), the assignment of its relative and absolute stereochemistry, and the resultant structural reassignment of the natural product previously represented as sultriecin (1), a phosphate versus sulfate monoester, are detailed. Studies with authentic material confirmed that phostriecin, but not sultriecin, is an effective and selective inhibitor of protein phosphatase 2A (PP2A) defining a mechanism of action responsible for its antitumor activity. The extension of the studies to the synthesis and evaluation of a series of key synthetic analogues is disclosed that highlights the importance of the natural product phosphate monoester (vs sulfate or free alcohol, both inactive and >250-fold), the α,β-unsaturated lactone (12-fold), and the hydrophobic Z,Z,E-triene tail (C12-C22, ca. 200-fold) including the unique importance of its unsaturation (50-fold, and no longer PP2A selective).

subject areas

  • Alkenes
  • Alkynes
  • Antineoplastic Agents
  • Humans
  • Lactones
  • Organophosphates
  • Protein Phosphatase 2
  • Stereoisomerism
scroll to property group menus

Identity

PubMed Central ID

  • PMC2978778

International Standard Serial Number (ISSN)

  • 0022-3263

Digital Object Identifier (DOI)

  • 10.1021/jo1010203

PubMed ID

  • 20669916
scroll to property group menus

Additional Document Info

start page

  • 7505

end page

  • 7513

volume

  • 75

issue

  • 22

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support