3 years ago

A New Approach to Models of the 4,5-Dihydroxycyclopentenone Core of the Kodaistatins A–D: Elucidation of the Diol Configuration in Kodaistatin A

A New Approach to Models of the 4,5-Dihydroxycyclopentenone Core of the Kodaistatins A–D: Elucidation of the Diol Configuration in Kodaistatin A
Reinhard Brückner, David Peter
The kodaistatins A–D are strongly anti-diabetic natural products from Aspergillus terreus that hold some promise of a novel diabetes cure. However, considerations of that kind face two drawbacks: 1) The kodaistatins A–D contain a heavily substituted pulvinone/cyclopentenone combination; 2) they are 1,2-diols, the 3D structures of which have not been assigned yet. However, we can exclude two of the four possible stereostructures. We conclude that kodaistatin A is a trans-, not a cis-diol from NMR comparisons with a pair of cis, trans-isomeric kodaistatin models, which we synthesized in 11 and 12 steps, respectively. The stereocenters of the diol moiety arose from stereocomplementary, highly diastereoselective aldol additions of a lithium enolate or the corresponding silyl ketene acetal. The cyclopentenone moieties stemmed from intramolecular aldol additions and ensuing dehydrations. The requisite enolates were obtained by the reduction of α-bromoketones with samarium diiodide. Aldols are the key: We determined the relative configuration in the diol moiety of the natural product kodaistatin A, an anti-diabetic lead, being trans. This follows from NMR comparisons with cis, trans-isomeric models, which we synthesized in 11–12 steps. Early-stage aldolizations ensured stereocomplementarity by using either a lithium enolate or an enol silane. Cyclopentanone formations by intramolecular aldol additions of samarium enolates ensued.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201701185

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.