3-Nitro-2-pyridinesulfenates as Efficient Solution- and Solid-Phase Disulfide Bond Forming Agents
3-Nitro-2-pyridinesulfenates as Efficient Solution- and Solid-Phase Disulfide Bond Forming Agents
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3-硝基-2-吡啶亚磺酸盐作为有效的溶液相和固相二硫键形成剂
DOI：
10.1002/chem.201700952
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发表时间：
2017
影响因子：
4.3
通讯作者：
Yoshio Hayashi
中科院分区：
文献类型：
--
作者：
Akihiro Taguchi;Kiyotaka Kobayashi;Akira Kotani;Kyohei Muguruma;Misaki Kobayashi;Kentarou Fukumoto;Kentaro Takayama;Hideki Hakamata;Yoshio Hayashi
本文根据3 -硝基- 2 -吡啶磺酸烷氧基（Npys - OR）氧化巯基的发现，报道了一种新的二硫生成剂。甲基3 -硝基- 2 -吡啶磺酸盐（Npys - OMe）是由3 -硝基- 2 -吡啶磺酰氯在一步反应中容易制备的，相对于Ag/AgCl，其还原峰电位（Epc）为- 0.541 V，以良好的线性形式（92%）产生环状非肽催产素，低聚物形成最少。固相Npys‐OMe在催产素合成中也表现出优异的效果。其他含二硫肽，如α‐人心房利钠肽和α‐concontoxin ImI，也被成功合成。在这些合成过程中，没有检测到蛋氨酸（Met）和色氨酸（Trp）残基或S‐乙酰氨基甲基（Acm）保护基团的副反应。这些结果表明，Npys - OMe或其固相类似物为区域选择性二硫键形成提供了一种新的策略，以帮助合成复杂的富含二硫的肽。
In this paper, a new disulfide‐forming agent based on the finding that alkoxy 3‐nitro‐2‐pyridinesulfenates (Npys‐OR) can oxidize thiol groups is reported. Methyl 3‐nitro‐2‐pyridinesulfenate (Npys‐OMe), which is easily prepared from 3‐nitro‐2‐pyridinesulfenyl chloride in a one‐step reaction and has a reduction peak potential (Epc) of −0.541 V versus Ag/AgCl, produces the cyclic nonapeptide oxytocin from its linear form in good yield (92 %) with minimal oligomer formation. Npys‐OMe in the solid phase also demonstrated excellent results in oxytocin synthesis. Other disulfide‐containing peptides, such as α‐human atrial natriuretic peptide and α‐conotoxin ImI, were also successfully synthesized. During these syntheses, no side reactions of methionine (Met) and tryptophan (Trp) residues or the S‐acetamidomethyl (Acm) protecting group were detected. These results suggested that Npys‐OMe or its solid‐phase analog provides a new strategy for regioselective disulfide bond formation to assist the synthesis of complex disulfide‐rich peptides.