The regioselective synthesis of multiple disulfide bonds in peptides has been a significant challenge in synthetic peptide chemistry. In this work, two disulfide bonds in peptides were regioselectively synthesized via an approach of MetSeO oxidation and deprotection reaction (SeODR), in which the first disulfide bond was constructed through oxidation of dithiol by MetSeO in a neutral buffer, and the second disulfide bond was then directly constructed through the deprotection of two Acm groups or one Acm group and one Thz group by MetSeO in acidic media. Synthesis of two disulfide bonds by the SeODR approach was achieved through a one-pot manner. Moreover, the SeODR approach is compatible with the synthesis of peptides containing methionine residues. Both H⁺ and Br^– drastically promoted the reaction rate of SeODR. The mechanistic picture for the SeODR approach was delineated, in which the formation of a stable Se–X–S bridge as the transition state plays a critical role. The SeODR approach was also utilized to construct the three disulfide bonds in linaclotide, conferring a reasonable yield.

中文翻译：

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L-蛋氨酸硒化物作为氧化和去保护试剂用于合成肽中的多个二硫键

肽中多个二硫键的区域选择性合成一直是合成肽化学中的重大挑战。在这项工作中，通过MetSeO氧化和脱保护反应（SeODR）的方法区域选择性合成了肽中的两个二硫键，其中第一个二硫键是通过MetSeO在中性缓冲液中氧化二硫醇构建的，第二个二硫键是然后通过MetSeO在酸性介质中对两个Acm基团或一个Acm基团和一个Thz基团进行脱保护直接构建。SeODR 方法通过一锅法实现了两个二硫键的合成。此外，SeODR 方法与含有蛋氨酸残基的肽的合成兼容。H ⁺和 Br ^–大大提高了SeODR的反应速率。描绘了 SeODR 方法的机理图，其中作为过渡态的稳定 Se-X-S 桥的形成起着关键作用。SeODR 方法也用于构建利那洛肽中的三个二硫键，获得了合理的产率。