Catalytic Dehydrative Peptide Synthesis with gem-Diboronic Acids
Catalytic Dehydrative Peptide Synthesis with gem-Diboronic Acids
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DOI：
10.1021/acscatal.9b03894
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发表时间：
2020-01-03
期刊：
影响因子：
12.9
通讯作者：
Takemoto, Yoshiji
中科院分区：
文献类型：
--
作者：
Michigami, Kenichi;Sakaguchi, Tatsuhiko;Takemoto, Yoshiji
烷烃-宝石-二硼酸已成为α-氨基酸脱水酰胺化的通用有机硼催化剂。具有B-C-B结构的苯酚取代的多硼催化剂在亲电体的差向异构化受到抑制的α-氨基酸的缩合中优于简单的芳基硼酸。偕-二硼酸催化与带有N-保护基团的各种O、N和S-官能化的α-氨基酸相容，包括肽合成中使用的常见氨基甲酸酯（Boc、Cbz、Fmoc）。N-三氟乙酰基保护使得能够在室温下进行前所未有的催化脱水肽合成。初步的机理研究揭示了羧酸结合性质的宝石-二硼酸，正交活化的羧酸芳基硼酸。偕二硼酸的独特反应性将为温和催化肽缩合开辟前景。
Alkane-gem-diboronic acids have emerged as versatile organoboron catalysts for dehydrative amidation of alpha-amino acids. A phenol-substituted multiboron catalyst with a B-C-B structure outperformed simple arylboronic acids in the condensation of alpha-amino acids with suppressed epimerization of electrophiles. gem-diboronic acid catalysis were compatible with various O, N, and S-functionalized alpha-amino acids bearing N-protecting groups including common carbamates used in peptide synthesis (Boc, Cbz, Fmoc). N-trifluoroacetyl protection enabled an unprecedented catalytic dehydrative peptide synthesis at room temperature. Preliminary mechanistic studies revealed carboxylate-binding nature of gem-diboronic acids, orthogonal to the activation of carboxylic acids by arylboronic acids. The distinctive reactivity of the gem-diboronic acids would open prospects for mild catalytic peptide condensation.