Fluoroolefin dipeptide isosteres — I.: The synthesis of Glyψ(CFCH)Gly and racemic Pheψy(CFCH)Gly
✍ Scribed by Thomas Allmendinger; Pascal Furet; Ernst Hungerbühler
- Publisher
- Elsevier Science
- Year
- 1990
- Tongue
- French
- Weight
- 255 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
The syntheses of Gly-Gly and racemic Phe-Gly fluoroolefin dipeptide isosteres are described, the firs-f examples of a new class of peptkle anabgues.
The use of non-hydrolyzable amide isosteres is an established approach 12 to overcoming one of the major drawbacks in the use of peptides as therapeutic agents, namely their rapid degradation by peptldases. One known approach is to use the trans-olefinic as amide mitic, which is geometrically equivalent to the amide bond in its most stable (transoid) conformation 3. Several contributions to the synthesis and application of this class of compounds 1 have been made 4.
Diiptide
X=H
2 X=F
We have calculated the molecular profiles of N-methyl acetamide, trans-2-butene and 2-fluoro-2(Z)-butane as simple models of the peptide bond (see figure ). Their compadson suggests that the fluomolefin unit is an even better Dreiding CPK AMIDE % -x-'6 Electrostatic potential Flgure 1: Dreiding and CPK-representation (standard geometries) and electrostatic potential profiles of N-methyl acetamide, transQ-butene and 2-fluoro-2(Z)-butene 5.