Histidine (His) racemizes with relative ease during peptide synthesis. One strategy to suppress this racemization is to protect the nitrogen atom of the imidazole moiety in His with a suitable protecting group. Among the numerous protecting groups that have already been tested, the p-methoxybenzyloxymethyl (PMBOM) group on the π-nitrogen atom effectively suppresses the racemization. However, a large-scale synthesis of N(π)-PMBOM-protected derivatives has hitherto been hampered by the requirement of a freshly prepared unstable reagent. Herein we report the synthesis of N(π)-2-naphthylmethoxymethyl (NAPOM)-protected His derivatives, which can be prepared on a gram scale and do not suffer from the aforementioned instability problems. Furthermore, these NAPOM-protected His derivatives suppress the racemization in Boc- and Fmoc-based peptide synthesis.

中文翻译：

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N（π）-2-萘甲氧基甲基保护的组氨酸：肽合成的可扩展，无消旋结构单元

组氨酸（His）在肽合成过程中相对容易消旋。抑制该消旋作用的一种策略是用合适的保护基保护His中咪唑部分的氮原子。在已经测试的众多保护基团中，π-氮原子上的对甲氧基苄氧基甲基（PMBOM）​​基团有效地抑制了消旋作用。然而，迄今为止，由于需要新鲜制备的不稳定试剂，阻碍了N（π）-PMBOM-保护的衍生物的大规模合成。在此我们报告N的合成（π）-2-萘甲氧基甲基（NAPOM）-保护的His衍生物，其可以克量级制备并且不遭受上述不稳定性问题。此外，这些NAPOM保护的His衍生物可抑制基于Boc和Fmoc的肽合成中的外消旋作用。