Electrophilic S-Trifluoromethylation of Cysteine Side Chains in α- and β-Peptides: Isolation of Trifluoro-methylated Sandostatin® (Octreotide) Derivatives
✍ Scribed by Stefania Capone; Iris Kieltsch; Oliver Flögel; Gerald Lelais; Antonio Togni; Dieter Seebach
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- German
- Weight
- 575 KB
- Volume
- 91
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
The new electrophilic trifluoromethylating 1‐(trifluoromethyl)‐benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF~3~ groups to the S‐atom of cysteine side chains of α‐ and β‐peptides (up to 13‐residues‐long; products 7–14). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2‐position). The products are purified by chromatography, and identified by ^1^H‐, ^13^C‐, and ^19^F‐NMR spectroscopy, by CD spectroscopy, and by high‐resolution mass spectrometry. The CF~3~ groups, thus introduced, may be replaced by H (Na/NH~3~), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin‐labelling, imaging, PET) are discussed.