The first sorbicillinoid alkaloids, the antileukemic sorbicillactones A and B, from a sponge-derived Penicillium chrysogenum strain
The first sorbicillinoid alkaloids, the antileukemic sorbicillactones A and B, from a sponge-derived Penicillium chrysogenum strain
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DOI：
10.1016/j.tet.2005.05.026
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发表时间：
2005-07-25
期刊：
影响因子：
2.1
通讯作者：
Müller, WEG
中科院分区：
文献类型：
--
作者：
Bringmann, G;Lang, G;Müller, WEG
从地中海海绵Irciniafasciculata分离的产黄青霉菌株的盐水培养产生了三个新的索比西林衍生的化合物（1-3），其结构主要通过2D NMR和质谱进行了鉴定。其中，索比西林内酯A（1）和B（2）是第一个含氮的索比西林类天然产物。化合物1是抗HIV活性的，并且它表现出对L5178 γ白血病细胞的强细胞毒活性，以及对宫颈癌HeLa S3细胞和嗜铬细胞瘤PC 12细胞的相对低的毒性。通过圆二色光谱的量子化学计算，确定了I和2的绝对构型。另一个分离的化合物，山梨乙烯酮（3），可能是通过与乙基乙烯基醚的Diels-Alder反应从山梨西林醇（4）衍生的人工产物。此外，还鉴定了已知的索比西林类真菌代谢物oxosorbicillinol（5）、索比西林（6）和bisvertinolone（7），以及生物碱野罂粟碱和罗奎福汀C。通过喂食实验，用C-13标记的前体研究了山梨酸内酯A（1）由乙酸、丙氨酸和蛋氨酸生物合成的起源。(c)2005爱思唯尔有限公司保留所有权利。
The saltwater culture of a Penicillium chrysogenum strain isolated from the Mediterranean sponge Ircinia fasciculata yielded three new sorbicillin-derived compounds (1-3), whose structures were elucidated mainly by 2D NMR and mass spectrometry. Among them, sorbicillactones A (1) and B (2) are the first sorbicillinoid natural products that contain nitrogen. Compound 1 is anti-HIV active and it exhibits a strong cytotoxic activity against L5178y leukemic cells, combined with a relatively low toxicity to cervical carcinoma HeLa S3 cells and pheochromocytoma PC 12 cells. The absolute configurations of I and 2 were elucidated by quantum chemical calculation of circular dichroism (CD) spectra. Another compound isolated, sorbivinetone (3), might be an artifact derived from sorbicillinol (4) by Diels-Alder reaction with ethyl vinyl ether. Furthermore, the known sorbicillinoid fungal metabolites oxosorbicillinol (5), sorbicillin (6), and bisvertinolone (7) were identified, as well as the alkaloids meleagrine and roquefortine C. The biosynthetic origin of sorbicillactone A (1) from acetate, alanine, and methionine was investigated by feeding experiments with C-13-labeled precursors. (c) 2005 Elsevier Ltd. All rights reserved.