Alaninyl variants of the marine natural product halocyamine A and their antibacterial properties

TETRAHEDRON

卷:74

Article

Fong, Hugo K. H.¹  Cadelis, Melissa M.¹  Brunel, Jean Michel²  Bourguet-Kondracki, Marie-Lise³  Barker, David¹  Copp, Brent R.¹ 

[1] Univ Auckland, Sch Chem Sci, Private Bay 92019, Auckland 1142, New Zealand

[2] Aix Marseille Univ, UMR Membranes & Cibles Therapeut MD1, INSERM U1261, Fac Pharm, 27 Bd Jean Moulin, F-13385 Marseille 5, France

[3] Museum Natl Hist Nat, Lab Mol Commun & Adaptat Microorganismes, UMR CNRS 7245, 57 Rue Cuvier CP 54, F-75005 Paris, France

关键词: Antibacterial;    Halocyamine;    Alaninyl analogue;    Enamide;    Marine natural product;   

DOI  :  10.1016/j.tet.2018.10.021

来源: Elsevier

【 摘 要 】

In an effort to explore the antibacterial potential of the marine natural product halocyamine A, a series of analogues including desbromo and alanine-substituted variants were synthesised and evaluated for biological activity against a panel of Gram-positive and -negative bacteria. The analogues were synthesised by a combination of solid-phase peptide synthesis and ruthenium complex/ytterbium triflate catalysed hydroamidation chemistry. Single alanine substitutions ([Ala(1)]-halocyamine A and [Ala(2)]-halocyamine A) gave only modest increases in activity towards Gram-positive bacteria, while di-alaninyl variants exhibited more potent activity with MIC values of 12.5-50 mu M towards the Gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis. A lipophilic trityl-protected intermediate of [Ala(2)]-halocyamine was the most active against the Gram-negative bacterium Escherichia coll. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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