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Electrophilic S ‐Trifluoromethylation of Cysteine Side Chains in α ‐ and β ‐Peptides: Isolation of Trifluoro‐methylated Sandostatin ® (Octreotide) Derivatives
Author(s) -
Capone Stefania,
Kieltsch Iris,
Flögel Oliver,
Lelais Gerald,
Togni Antonio,
Seebach Dieter
Publication year - 2008
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200890217
Subject(s) - chemistry , trifluoromethylation , electrophile , reagent , side chain , residue (chemistry) , trifluoromethyl , nuclear magnetic resonance spectroscopy , fast atom bombardment , cysteine , stereochemistry , mass spectrometry , combinatorial chemistry , organic chemistry , chromatography , alkyl , polymer , enzyme , catalysis
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.