In conventional solid-phase peptide synthesis (SPPS), α-amino groups are protected with alkoxycarbonyl groups (e.g., 9-fluorenylmethoxycarbonyl [Fmoc]). However, during SPPS, inherent side reactions of the protected amino acids (e.g., α-C racemization and aspartimide formation) generate by-products that are hard to remove. Herein, we report a thiol-labile amino protecting group for SPPS, the 2,4-dinitro-6-phenyl-benzene sulfenyl (DNPBS) group, which is attached to the α-amino group via a S–N bond and can be quantitatively removed in minutes under nearly neutral conditions (1 M p-toluenethiol/pyridine). The use of DNPBS greatly suppresses the main side reactions observed during conventional SPPS. Although DNPBS SPPS is not as efficient as Fmoc SPPS, especially for synthesis of long peptides, DNPBS and Fmoc are orthogonal protecting groups; and thus DNPBS SPPS and Fmoc SPPS can be combined to synthesize peptides that are otherwise difficult to obtain.

在传统的固相肽合成(SPPS)中，α-氨基被烷氧基羰基(例如，9-芴基甲氧基羰基[Fmoc])保护。然而，在 SPPS 过程中，受保护氨基酸的固有副反应（例如 α-C 外消旋和天冬酰亚胺形成）会产生难以去除的副产物。在此，我们报道了 SPPS 的硫醇不稳定氨基保护基团，即 2,4-二硝基-6-苯基-苯硫基 (DNPBS) 基团，该基团通过 S-N 键连接到 α-氨基基团，并且可以在近中性条件下（1 M对甲苯硫醇/吡啶）在几分钟内即可定量去除。DNPBS 的使用极大地抑制了传统 SPPS 期间观察到的主要副反应。虽然DNPBS SPPS不如Fmoc SPPS有效，特别是对于长肽的合成，DNPBS和Fmoc是正交保护基团；因此，DNPBS SPPS 和 Fmoc SPPS 可以组合来合成难以获得的肽。