Mutacin 1140 (MU1140) is a naturally occurring lantibiotic derived from posttranslational modifications of a ribosomally synthesized peptide during the fermentation of a bacterium called Streptococcus mutans, the etiological agent of dental cavities. A practical approach for chemically synthesizing lantibiotics would be a valuable tool to expand the MU1140 library with additional semisynthetic analogs. In turn, an expanded library may prove useful to explore additional therapeutic indications for this pipeline of novel compounds. In this work, orthogonally protected lanthionine analogs were synthesized via an aziridine ring opening strategy. This lanthionine was utilized to synthesize a cysteamine (Cya) instead of the (S)‐aminovinyl‐D‐cysteine (AviCys) that is naturally found in MU1140. The Cya containing bicyclic C/D ring of MU1140 was synthesized by Fmoc solid‐phase peptide synthesis (SPPS). The linear peptides were synthesized using OPfp ester derivatives and using various common coupling reagents such as COMU and TCTU. The linear peptide was intracyclized with DEPBT to construct the so‐called bicyclic ring C/D. This is the first report on the complete chemical synthesis of the bicyclic C/D ring of a MU1140 analog using orthogonally protected lanthionines using SPPS.

中文翻译：

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通过固相环内化完全合成具有正交保护的羊毛硫氨酸的诱变类似物的双环。

Mutacin 1140（MU1140）是一种天然存在的羊毛硫抗生素，其源于核糖体合成肽的翻译后修饰，该细菌在名为“变形链球菌”（Streptococcus mutans）的细菌发酵过程中发生了变种，该细菌是蛀牙的病因。化学合成羊毛硫抗生素的实用方法将是扩展MU1140文库与其他半合成类似物的有价值的工具。反过来，扩展的文库可能被证明对探索这种新型化合物的治疗指征有用。在这项工作中，通过氮丙啶开环策略合成了正交保护的羊毛硫氨酸类似物。该羊毛硫氨酸被用于合成半胱胺（Cya）而不是（S）-氨基乙烯基-DMU1140中自然存在的半胱氨酸（AviCys）。通过Fmoc固相肽合成（SPPS）合成了MU1140的含Cya双环C / D环。线性肽是使用OPfp酯衍生物并使用各种常见的偶联剂（例如COMU和TCTU）合成的。将线性肽与DEPBT进行环内环化，以构建所谓的双环C / D。这是有关使用SPPS正交保护的羊毛硫氨酸完全合成MU1140类似物双环C / D环的第一份报告。