Solid-phase synthesis of fusaricidin/LI-F class of cyclic lipopeptides: Guanidinylation of resin-bound peptidyl amines.
Solid-phase synthesis of fusaricidin/LI-F class of cyclic lipopeptides: Guanidinylation of resin-bound peptidyl amines.
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DOI：
10.1002/bip.22186
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发表时间：
2013-04
期刊：
影响因子：
2.9
通讯作者：
Cudic, Predrag
中科院分区：
文献类型：
--
作者：
Bionda, Nina;Pitteloud, Jean-Philippe;Cudic, Predrag
关键词：
杀镰孢菌素/LI-F和相关的环脂肽代表了一类有趣的新的抗菌肽，具有应对细菌抗生素耐药性挑战的潜力。我们以前的研究（N。Bionda等人，ChemMedChem 2012，7，871-882）揭示了位于这些环状脂肽的疏水尾末端的胍基对于它们的抗菌活性的重要性。因此，设计一种合成策略，将允许胍功能纳入其结构是特别实际的重要性。由于适当保护的胍基脂肪酸结构单元不可商购获得，因此我们针对胍基化杀镰孢菌素/LI-F类似物的策略包括固相合成具有末端氨基的无规尾的环状脂肽前体，然后将其转化为相应的胍。为了找到这种转换的最佳方法，我们已经检查了常用的胍基化试剂的条件下兼容的标准固相肽合成。实验结果表明，N，N′-di-Boc-N″-triflylguanidine在固相合成杀镰孢菌素/LI-F类环脂肽中的优越性。三氟甲酰基胍试剂得到一个单一的单胍基化的产品在良好的产率独立的类型的固体支持。
Fusaricidins/LI-Fs and related cyclic lipopeptides represent an interesting new class of antibacterial peptides with the potential to meet the challenge of antibiotic resistance in bacteria. Our previous study (N. Bionda et al. ChemMedChem 2012, 7, 871-882) revealed the significance of the guanidinium group located at the termini of the lipidic tails of these cyclic lipopeptides for their antibacterial activities. Therefore, devising a synthetic strategy that will allow incorporation of guanidinium functionality into their structure is of particular practical importance. Since appropriately protected guanidino fatty acid building blocks are not commercially available, our strategy toward guanidinylated fusaricidin/LI-F analogs include solid-phase synthesis of a cyclic lipopeptide precursor possessing a lipidic tail with a terminal amino group followed by its conversion into corresponding guanidine. To find the optimal method for this conversion, we have examined commonly used guanidinylation reagents under the conditions compatible with standard solid-phase peptide synthesis. Described experimental results demonstrated superiority of N,N′-di-Boc-N″-triflylguanidine in solid-phase preparation of fusaricidin/LI-F class of cyclic lipopeptides. The triflylguanidine reagent gave a single monoguanidinylated product in excellent yield independently of the type of solid-support.
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