Bertin Matthew J, Roduit Alexandre F, Sun Jiadong, Alves Gabriella E, Via Christopher W, Gonzalez Miguel A, Zimba Paul V, Moeller Peter D R
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Center for Coastal Studies and Department of Life Sciences, Texas A&M Corpus Christi, 6300 Ocean Drive, Corpus Christi, TX 78412, USA.
Mar Drugs. 2017 Jun 30;15(7):206. doi: 10.3390/md15070206.
Bioassay-guided isolation of the lipophilic extract of bloom material led to the purification and structure characterization of two new hybrid polyketide-non-ribosomal peptide (PKS-NRPS) macrocyclic compounds, tricholides A and B ( and ). A third macrocyclic compound, unnarmicin D (), was identified as a new depsipeptide in the unnarmicin family, given its structural similarity to the existing compounds in this group. The planar structures of - were determined using 1D and 2D NMR spectra and complementary spectroscopic and spectrometric procedures. The absolute configurations of the amino acid components of - were determined via acid hydrolysis, derivitization with Marfey's reagent and HPLC-UV comparison to authentic amino acid standards. The absolute configuration of the 3-hydroxydodecanoic acid moiety in was determined using a modified Mosher's esterification procedure on a linear derivative of tricharmicin () and additionally by a comparison of C NMR shifts of to known depsipeptides with -hydroxy acid subunits. Tricholide B () showed moderate cytotoxicity to Neuro-2A murine neuroblastoma cells (EC: 14.5 ± 6.2 μM).
对水华中亲脂性提取物进行生物测定导向的分离，得到了两种新的杂合聚酮化合物 - 非核糖体肽（PKS-NRPS）大环化合物三枝曲菌素A和B（图1和图2）的纯化和结构表征。第三种大环化合物，非那米星D（图3），由于其与该组中现有化合物的结构相似性，被鉴定为非那米星家族中的一种新的缩肽。通过一维和二维核磁共振光谱以及补充的光谱和波谱方法确定了化合物1-3的平面结构。通过酸水解、用Marfey试剂衍生化以及与真实氨基酸标准品进行高效液相色谱 - 紫外比较，确定了化合物1-3中氨基酸组分的绝对构型。使用改良的Mosher酯化方法对三枝曲菌素（图4）的线性衍生物进行测定，并通过比较化合物3与具有β-羟基酸亚基的已知缩肽的碳核磁共振化学位移，确定了化合物3中3-羟基十二烷酸部分的绝对构型。三枝曲菌素B（图2）对Neuro-2A小鼠神经母细胞瘤细胞显示出中等细胞毒性（半数有效浓度：14.5±6.2μM）。
