Electrophilic S-Trifluoromethylation of Cysteine Side Chains in alpha- and beta-Peptides: Isolation of Trifluoronethylated Sandostatin (R) (Octreotide) Derivatives

The new electrophilic trifluormethylating 1-(trifluoromethyl)-benziodoxole reagents A and B (Scheme I) have been used to selectively attach CF3 groups to the Satom of cysteine side chains of alpha- and beta-peptides (up to 13-residues-ling: products 7-14). Other functional groups in the substrates (...

Full description

Saved in:
Bibliographic Details
Published inHelvetica chimica acta Vol. 91; no. 11; pp. 2035 - 2056
Main Authors Capone, Stefania, Kieltsch, Iris, Floegel, Oliver, Lelais, Gerald, Togni, Antonio, Seebach, Dieter
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 01.01.2008
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
MEDICINAL CHEMISTRY
CHIRAL BUILDING-BLOCKS
ARNDT-EISTERT REACTION
AMINO-ACIDS
CLICK CHEMISTRY
PROTEOLYTIC STABILITY
(S)-4,4,4-TRIFLUORO-3-HYDROXYBUTANOIC ACID
FLUORO COMPLEX
ENANTIOSELECTIVE HALOGENATION
EFFICIENT METHOD
Online AccessGet full text

Cover

More Information
Summary:The new electrophilic trifluormethylating 1-(trifluoromethyl)-benziodoxole reagents A and B (Scheme I) have been used to selectively attach CF3 groups to the Satom of cysteine side chains of alpha- and beta-peptides (up to 13-residues-ling: 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 H-1-, C-13-, and F-19-NMR spectroscopy, by CD spectroscopy, and by high-resolution mass spectrometry. The CF3 groups, thus introduced, may be replaced by H (Na/NH3), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin-labelling imaging, PET) are discussed.
ISSN:0018-019X
1522-2675
DOI:10.1002/hlca.200890217