Residue‐Selective C−H Sulfenylation Enabled by Acid‐Activated <i>S</i>‐Acetamidomethyl Cysteine Sulfoxide with Application to One‐Pot Stapling and Lipidation Sequence
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- Kento Ohkawachi
- Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences Tokushima University Tokushima 770-8505 Japan
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- Kaito Anzaki
- Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences Tokushima University Tokushima 770-8505 Japan
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- Daishiro Kobayashi
- Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences Tokushima University Tokushima 770-8505 Japan
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- Ryuji Kyan
- Faculty of Pharmacy and Pharmaceutical Sciences Fukuyama University Hiroshima 729-0292 Japan
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- Takuma Yasuda
- Department of Diabetes Endocrinology and Nutrition Graduate School of Medicine Kyoto University Kyoto 606-8507 Japan
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- Masaya Denda
- Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences Tokushima University Tokushima 770-8505 Japan
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- Norio Harada
- Department of Diabetes Endocrinology and Nutrition Graduate School of Medicine Kyoto University Kyoto 606-8507 Japan
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- Akira Shigenaga
- Faculty of Pharmacy and Pharmaceutical Sciences Fukuyama University Hiroshima 729-0292 Japan
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- Nobuya Inagaki
- Department of Diabetes Endocrinology and Nutrition Graduate School of Medicine Kyoto University Kyoto 606-8507 Japan
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- Akira Otaka
- Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences Tokushima University Tokushima 770-8505 Japan
説明
<jats:title>Abstract</jats:title><jats:p>A tyrosine (Tyr)‐ or tryptophan (Trp)‐selective metal‐free C−H sulfenylation reaction using an acid‐activated <jats:italic>S</jats:italic>‐acetamidomethyl cysteine (Cys) sulfoxide, Cys(Acm)(O), has been achieved. The dually protonated intermediate produced from Cys(Acm)(O) under acidic conditions allows the sulfenylation of Tyr. Significantly, the reaction in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) mainly affords a Cys‐Tyr‐linked peptide even in the presence of Trp residues. In contrast, a Cys‐Trp‐linked peptide was selectively obtained from the reaction in the presence of guanidine hydrochloride (Gn ⋅ HCl) under acidic conditions. Established Tyr‐ and Trp‐selective sulfenylation methods were used in the Cys‐Tyr stapling and Trp lipidation of glucagon‐like peptides <jats:bold>1</jats:bold> in a one‐pot/stepwise manner. Investigation of the mechanism showed that orbital‐ and charge‐controlled reactions are responsible for the Trp and Tyr selectivity, respectively.</jats:p>
収録刊行物
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- Chemistry – A European Journal
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Chemistry – A European Journal 29 (26), 2023-04-04
Wiley