Iodine Oxidation of S-Trityl- and S-Acetamidomethyl-cysteine-peptides Containing Tryptophan: Conditions Leading to the Formation of Tryptophan-2-thioethers
✍ Scribed by Peter Sieber; Bruno Kamber; Bernhard Riniker; Werner Rittel
- Publisher
- John Wiley and Sons
- Year
- 1980
- Tongue
- German
- Weight
- 351 KB
- Volume
- 63
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
Cystine peptides are conveniently prepared from S‐acetamidomethyl‐ or S‐trityl‐protected cysteine derivatives by direct oxidation with iodine. Since the reaction proceeds through the formation of sulfenyl iodides, these highly reactive groups may substitute the indole ring of tryptophan residues, resulting in the formation of 2‐thioethers. During the synthesis of the peptide hormone somatostatin, we investigated this possible side reaction. By‐products of the tryptophan‐2‐thioether type can be produced under conditions which lead to a marked retardation of the disulfide bond formation. The largest amount of these compounds were formed when the oxidation was carried out in 90% aqueous trifluoroethanol.
In model peptides in which tryptophan and cysteine residues were separated by 1 to 4 glycine residues, the ring size of the resulting thioether exerted a strong influence on the yield: in peptides with 1 and 2 glycines, only dimeric disulfides were formed. Incorporation of 3 and 4 glycine residues gave thioethers in yields of about 40% and 70% respectively. Conversely, under normal conditions of iodine oxidation, when disulfides are rapidly formed from the S‐acetamidomethyl‐ or S‐tritylcysteine residues, tryptophan‐2‐thioethers are produced only in insignificant amounts or not at all.