Orthogonally protected lanthionines: Synthesis and use for the solid-phase synthesis of an analogue of nisin ring C
Orthogonally protected lanthionines: Synthesis and use for the solid-phase synthesis of an analogue of nisin ring C
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DOI：
10.1021/jo048222t
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发表时间：
2005-04-01
影响因子：
3.6
通讯作者：
Tabor, AB
中科院分区：
文献类型：
--
作者：
Bregant, S;Tabor, AB
硫氨酸是胱氨酸的硫醚类似物，是l抗生素的关键组成部分，l抗生素是一类经过修饰的肽，在侧链之间的翻译后修饰产生多个硫醚桥。它也被用作药用活性肽的构象约束。我们探索了两种合成途径，得到了由Alloc/allyl和Fmoc基团正交保护的镧系硫氨酸。一种方法是利用氨基甲酸酯保护的碘丙氨酸产生非对映异构体的混合物，另一种方法是利用三基保护的碘丙氨酸，通过Mitsunobu反应形成，在完全的区域和非对映选择性下产生单一所需的硫氨酸。然后，我们使用这种正交保护的硫代氨酸在固相合成含有其环c的nisin片段的类似物。结合的硫代氨酸单元的烯丙基和Alloc基团的化学选择性去保护之后，在树脂上进行区域和立体选择性环化，得到所需的硫代氨酸桥接肽。
Lanthionine, a thioether analogue of cystine, is a key component of the lantibiotics, a family of modified peptides bearing multiple thioether bridges resulting from posttranslational modifications between side chains. It is also used as a conformational constraint in medicinally active peptides. We have explored two synthetic routes to give lanthionine, orthogonally protected with Alloc/allyl and Fmoc groups. One route utilized a carbamate-protected iodoalanine that yielded a mixture of diastereoisomers, and one utilized a trityl-protected iodoalanine, formed via a Mitsunobu reaction, that gave the single desired lanthionine, in complete regio-and diastereoselectivity. We then used this orthogonally protected lanthionine in the solid-phase synthesis of an analogue of a fragment of nisin containing its ring C. The chemoselective deprotection of the allyl and Alloc groups of the incorporated lanthionine unit was followed by regio- and stereoselective cyclization on resin to give the desired lanthionine-bridged peptide.