A New Efficient Method for S–CH2–S Bond Formation and Its Application to a Djenkolic Acid-Containing Cyclic Enkephalin Analog

An efficient methylene insertion reaction to construct an S–CH2–S bridge between two cysteine residues occurred when the thiol-protecting dimethylphosphinothioyl (Mpt) group of Z–Cys(Mpt)–OMe was removed with tetrabutylammonium fluoride hydrate in CH2Cl2. The thiol-free form gave similar results, al...

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Published inBulletin of the Chemical Society of Japan Vol. 72; no. 4; pp. 829 - 838
Main Authors Ueki, Masaaki, Ikeo, Takayoshi, Hokari, Kumiko, Nakamura, Keiko, Saeki, Akihiko, Komatsu, Hiroshi
Format Journal Article
LanguageEnglish
Published TOKYO The Chemical Society of Japan 01.04.1999
Chemical Soc Japan
Chemical Society of Japan
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
PEPTIDES
REMOVAL
AFFINITY
PHOSPHINOTHIOYLAMINO ACIDS
PHOSPHINYLTHIOYLAMINO
TRISULFIDE
CYSTEINE
THIOL-PROTECTING GROUP
DISULFIDE
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Summary:An efficient methylene insertion reaction to construct an S–CH2–S bridge between two cysteine residues occurred when the thiol-protecting dimethylphosphinothioyl (Mpt) group of Z–Cys(Mpt)–OMe was removed with tetrabutylammonium fluoride hydrate in CH2Cl2. The thiol-free form gave similar results, albeit the yields were somewhat lower. In both cases, the best yields were obtained using 2 molar amounts of the reagent. Higher amounts of the reagent reduced the yield because of dehydroalanine formation. In the case of penicillamine, the thiol-free form was better in reactivity than the S-Mpt form, which required double the amount of the reagent to give the same yield. The reaction was successfully used in a synthesis of a cyclic enkephalin analog with the S–CH2–S bridge.
ISSN:0009-2673
1348-0634
DOI:10.1246/bcsj.72.829