LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Carbain, Benoit (2010)
Languages: English
Types: Doctoral thesis
Subjects: QD
Influenza virus infection and the shikimic acid pathway are two of many examples of microbe-host interactions and microbial biosynthetic pathways that are interesting for investigation by means of small molecules. A particularly interesting structural motif common to both is the cyclohexenecarboxylic acid. In the former, this structural motif has been employed as a mimetic of the sialyl cation intermediate and forms the scaffold of the anti-influenza drug and neuraminidase inhibitor Oseltamivir (or TamifluTM). In the latter pathway, crucial modifications towards aromatic amino acids are carried out via shikimic acid, a cyclohexenecarboxylic acid, as a substrate. A straightforward method to replace the carboxylate moiety in such structures with a phosphonate would provide access to a wide variety of mimetics, for instance monoesters, that still retain a negative charge under physiological conditions usually required for bioactivity. The aim of this research project was to develop an efficient synthesis of the cyclohexenephosphonate scaffold from chiral pool precursors via two key steps, a Hunsdiecker-Barton iododecarboxylation followed by a palladiummediated coupling step to introduce the phosphonate moiety, thus giving a convenient access to interesting bioactive molecules. This approach has successfully been applied to the shikimic acid to afford ‘phospha’-shikimic acids and 3-dehydro-‘phospha’-shikimic acids, and further development of this strategy has led to the synthesis of ‘phospha’-Tamiflu and its derivatives from an Oseltamivir precursor.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • Experimental section...........................................................................................80 III.1. General procedures.............................................................................................80 III.2. Synthetic procedures and compound characterization.......................................81 O
  • No related research data.
  • No similar publications.

Share - Bookmark

Download from

Cite this article