Solid Supported Chemical Syntheses of Both Components of the Lantibiotic Lacticin 3147
Solid Supported Chemical Syntheses of Both Components of the Lantibiotic Lacticin 3147
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DOI：
10.1021/ja206017p
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发表时间：
2011-09-14
影响因子：
15
通讯作者：
Vederas, John C.
中科院分区：
文献类型：
--
作者：
Liu, Wei;Chan, Alice S. H.;Vederas, John C.
抗生素是由细菌产生的抗菌肽。一些用于食品保存，而另一些则由于对当前抗生素耐药的微生物具有活性而具有治疗潜力。它们通过核糖体合成和翻译后修饰，丝氨酸和苏氨酸残基脱水，然后半胱氨酸的硫醇攻击，分别形成单硫的羊硫氨酸和甲基兰硫氨酸环。多肽类似物的化学合成是验证立体化学和获取构效关系的有效方法。然而，由于生成具有正交保护和良好立体化学控制的羊毛硫醚和甲基羊毛硫氨酸的问题，固体支撑合成抗生素一直是困难的。我们报道了双组分抗生素Lacticin 3147的两种多肽的固相合成。连续的和互锁的环系统都是在树脂上合成的，因此为这一系列天然产品提供了一种通用的方法。
Lantibiotics are antimicrobial peptides produced by bacteria. Some are employed for food preservation, whereas others have therapeutic potential due to their activity against organisms resistant to current antibiotics. They are ribosomally synthesized and posttranslationally modified by dehydration of serine and threonine residues followed by attack of thiols of cysteines to form mono sulfide lanthionine and methyllanthionine rings, respectively. Chemical synthesis of peptide analogues is a powerful method to verify stereochemistry and access structure-activity relationships. However, solid supported synthesis of lantibiotics has been difficult due to problems in generating lanthionines and methyllanthionines with orthogonal protection and good stereochemical control. We report the solid-phase syntheses of both peptides of a two-component antibiotic, lacticin 3147. Both successive and interlocking ring systems were synthesized on-resin, thereby providing a general methodology for this family of natural products.