MacMillan John B, Ernst-Russell Michael A, de Ropp Jeffrey S, Molinski Tadeusz F
Department of Chemistry, One Shields Avenue, University of California, Davis, California 95616, USA.
J Org Chem. 2002 Nov 15;67(23):8210-5. doi: 10.1021/jo0261909.
The structures of lipopeptides lobocyclamides A (1), B (2), and C (3) were solved using a combination of mass spectrometry, 2D NMR spectroscopy, and degradative analysis. Lobocyclamides B and C are the first peptides reported with the unusual amino acid 4-hydroxythreonine and also incorporate the rare homologous long-chain beta-amino acids 3-aminooctanoic acid and 3-aminodecanoic acid, respectively. The absolute configurations of the amino acid residues in each compound were assigned, after acid hydrolysis, by either direct chiral HPLC comparison with authentic standards or by prior derivatization by Marfey's method and reversed-phase HPLC. Both compounds exhibited moderate antifungal activity against a panel of Candida spp., including two fluconazole-resistant strains. When tested as a mixture, lobocyclamides A and B displayed synergistic in vitro antifungal activity, a phenomenon noted earlier for the related peptides laxaphycins A and B.
利用质谱、二维核磁共振光谱和降解分析相结合的方法解析了脂肽环洛酰胺A（1）、B（2）和C（3）的结构。环洛酰胺B和C是首次报道的含有不寻常氨基酸4-羟基苏氨酸的肽，并且分别还包含罕见的同源长链β-氨基酸3-氨基辛酸和3-氨基癸酸。在酸水解后，通过与真实标准品直接进行手性高效液相色谱比较，或通过马尔费方法进行预先衍生化并结合反相高效液相色谱，确定了每种化合物中氨基酸残基的绝对构型。这两种化合物对一组念珠菌属菌株均表现出中等抗真菌活性，包括两株氟康唑耐药菌株。当作为混合物进行测试时，环洛酰胺A和B表现出协同体外抗真菌活性，这一现象在相关肽类松弛藻毒素A和B中也曾被观察到。
