Han Bingnan, Goeger Doug, Maier Claudia S, Gerwick William H
College of Pharmacy and Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
J Org Chem. 2005 Apr 15;70(8):3133-9. doi: 10.1021/jo0478858.
Four new depsipeptides have been isolated from the marine cyanobacterium Lyngbya semiplena collected from Papua New Guinea. The amino and hydroxy acid partial structures of wewakpeptins A-D (1-4) were elucidated through extensive spectroscopic techniques, including HR-FABMS, 1D (1)H and (13)C NMR, as well as 2D COSY, HSQC, HSQC-TOCSY, and HMBC spectra. The sequence of the residues was determined through a combination of multifaceted approaches including ESI-MS/MS, HMBC, ROESY, and a modified 1D HMBC experiment. The absolute stereochemistry of each residue was determined by chiral HPLC and chiral GC-MS methods. The wewakpeptins represent an unusual arrangement of amino and hydroxy acid subunits relative to known cyanobacterial peptides and possess a bis-ester, a 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya) or 2,2-dimethyl-3-hydroxyoctanoic acid (Dhoaa) residue, and a diprolyl group reminiscent of dolastatin 15. Wewakpeptin A and B were the most cytotoxic among these four depsipeptides with an LC(50) of approximately 0.4 muM to both the NCI-H460 human lung tumor and the neuro-2a mouse neuroblastoma cell lines.
从采集自巴布亚新几内亚的海洋蓝藻半丰满鞘丝藻中分离出了四种新的缩肽。通过包括高分辨快原子轰击质谱（HR-FABMS）、一维氢谱（¹H NMR）和碳谱（¹³C NMR）以及二维化学位移相关谱（COSY）、异核单量子相干谱（HSQC）、异核单量子相干转移相关谱（HSQC-TOCSY）和异核多键相关谱（HMBC）等广泛的光谱技术，阐明了韦瓦克缩肽A-D（1-4）的氨基酸和羟基酸部分结构。通过包括电喷雾串联质谱（ESI-MS/MS）、HMBC、旋转核Overhauser效应谱（ROESY）和改良的一维HMBC实验等多方面方法的组合确定了残基序列。通过手性高效液相色谱（HPLC）和手性气相色谱-质谱（GC-MS）方法确定了每个残基的绝对立体化学。相对于已知的蓝藻肽，韦瓦克缩肽呈现出氨基酸和羟基酸亚基的不寻常排列，并具有一个双酯、一个2,2-二甲基-3-羟基-7-辛炔酸（Dhoya）或2,2-二甲基-3-羟基辛酸（Dhoaa）残基，以及一个让人联想到多拉司他汀15的二脯氨酰基。在这四种缩肽中，韦瓦克缩肽A和B对NCI-H460人肺肿瘤细胞系和神经-2a小鼠神经母细胞瘤细胞系的细胞毒性最强，半数致死浓度（LC₅₀）约为0.4 μM。
