Total Synthesis of Viridiofungins A and B

  • Author: ChemistryViews.org
  • Published: 26 April 2021
  • Copyright: Wiley-VCH GmbH
  • Associated Societies: American Chemical Society (ACS), USA
thumbnail image: Total Synthesis of Viridiofungins A and B

Viridiofungins A and B (pictured, R = OH for viridiofungin A, R = H for viridiofungin B) are part of a family of bioactive alkyl citrate natural products and were first isolated from a fungus. The compounds feature a fairly long alkyl chain and a citric acid unit and can be challenging to synthesize in a stereoselective manner. Existing syntheses of viridiofungin A have 16 or more steps [1].


Mark A. Rizzacasa, The University of Melbourne, Victoria, Australia, and colleagues have developed a highly stereoselective total synthesis of viridiofungins A and B via a common β-lactone intermediate in 13 steps. The team started from commercially available (S)-(+)-γ-hydroxymethyl-γ-butyrolactone, which was protected and then subjected to a formal [2+2] cycloaddition with di-t-butylacetylene dicarboxylate. The resulting cyclobutene diester underwent an HF-mediated rearrangement to give a bicyclic lactone. This lactone was converted to the desired common alkene-functionalized β-lactone intermediate via a ring-opening, a lactonization, and an alkene isomerization.


The team subjected this intermediate to an olefin cross-metathesis reaction to introduce the side chain of the target compounds. Then, a ring-opening of the β-lactone was used to form the amide unit and introduce the correct aromatic substituent for viridiofungin A or B, and a final deprotection step gave the desired products in high yields. According to the researchers, the stable β-lactone intermediate could also be useful as a precursor for other viridiofungins or their analogues for further studies.



Reference

 

 

Article Views: 623

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more

Follow on Facebook Follow on Twitter Follow on YouTube Follow on LinkedIn Follow on Instagram RSS Sign up for newsletters

Magazine of Chemistry Europe (16 European Chemical Societies) published by Wiley-VCH