Synthesis and biological evaluation of gramicidin S-inspired cyclic mixed α/β-peptides.

Matthijs van der Knaap, Fatih Basalan, Henny C van de Mei, Henk J Busscher, Gijsbert A van der Marel, Herman S Overkleeft, Mark Overhand

Index: Chem. Biodivers. 9(11) , 2494-506, (2012)

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Abstract

Via a Mannich reaction involving a dibenzyliminium species and the titanium enolates of Evans' chiral acylated oxazolidinones the β(2)-amino acids (R)- and (S)-Fmoc-β(2)homovaline and (R)-Fmoc-β(2)homoleucine are synthesized. These building blocks were used, in combination with commercially available α- and β(3)-amino acids, for the synthesis of the cyclo-(αβ(3)αβ(2)α)(2) peptide 2 and the cyclo-(αβ(2)αβ(3)α)(2) peptides 3-5. The peptides 2-5 were screened for their ability to inhibit a small panel of Gram-negative and Gram-positive bacterial strains.Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.