Efficient oxidation of N-protected tryptophan and tryptophanyl-dipeptides by in situ generated dimethyldioxirane provides hexahydropyrroloindoline-containing synthons suitable for peptide synthesis and subsequent tryptathionylation

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• 作者：Antoine Blanc ; Fan Xia ; Mihajlo Todorovic ; David M. Perrin
• 关键词：Dimethyldioxirane ; Tryptophan oxidation ; 3a ; Hydroxypyrrolo[2 ; 3 ; b]indoline ; Peptide synthesis
• 刊名：Amino Acids
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：49
• 期：2
• 页码：407-414
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Analytical Chemistry; Biochemical Engineering; Life Sciences, general; Proteomics; Neurobiology;
• 出版者：Springer Vienna
• ISSN：1438-2199
• 卷排序：49

文摘

A series of hydroxypyrroloindoline (Hpi) containing dipeptides along with the corresponding monomeric Hpi-α-amino acid (Hpi-2-carboxylate), were prepared by reacting a series of Nα-protected-tryptophans in aqueous or biphasic [water/cyclopentyl methyl ether (CPME)] solutions containing Oxone® (potassium peroxymonosulfate) and acetone. This procedure avoids the tedious distillation of unstable dimethyldioxirane (DMDO), which is commonly used to oxidize indoles. Monomers Nα-Boc-Hpi-OH and Nα-Fmoc-Hpi-OH were readily incorporated by solid-phase peptide synthesis (SPPS) into a peptide containing a cysteine; in trifluoroacetic acid (TFA), the Hpi underwent intramolecular dehydrative condensation with the cysteine thiol to afford the anticipated tryptathionine crosslink. This eco- and user-friendly oxidative methodology greatly simplifies the synthesis of Hpi derivatives while enabling the synthesis of tryptathionine crosslinks characteristic of phalloidin and amanitin, two potent peptide toxins of present interest.