Efficient Syntheses of Permethylated Derivatives of Neolamellarin A,a Pyrrolic Marine Natural Product

The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellarin-like phenolic pyrrole compounds, which can inhibit hypoxia-induced HIF-1 activation. Many pyrrole-derived lamellarin-like alkaloids show potent MDR reversing activity. In this study, five permethylated derivatives of neolamellarin A were synthesized with their MDR reversing activity studied in order to identify new MDR reversal agents. A convergent strategy was adopted to synthesize the permethylated derivatives of neolamellarin A. Pyrrole was first converted into a corresponding N-trisisopropylsilyl （TIPS）-substituted derivative, then through iodination afforded 3,4-diiodinated pyrrole compound. The key intermediate, 3,4-disubstituent-lH-pyrrole, was obtained through desilylation of 3,4-disubstituent-l-TIPS pyrrole, which was prepared from 3,4-diiodinated pyrrole derivative and aryl boronic acid ester through Suzuki cross-coupling reaction between them. Then, the intermediate, 3,4-disubstituent-lH-pyrrole, reacted with fresh phenylacetyl chloride under n-BuLi/THF condition afforded the target compounds. Finally, we obtained five novel pyrrolic com- pounds, permethylated derivatives ofneolamellarin A 16a-e, in 30%-37% yield through five step reactions. The bioactivity testing of these compounds are in process.

Synthesis and Neuroprotective Activity of Neolamellarin A Analogues

Alkaloids are a class of natural products with a wide range of biological activities. Due to the special living environment, the alkaloids from marine sponges have exhibited different biological activities and promising medical application potential. Neolamellarin A is a marine alkaloid possessing bisaryl-pyrrole structural features. Here, the synthesis of 12 different 3,4-bisaryl-N-alkylated permethylated analogues of neolamellarin A and their outstanding neuroprotective activity in PC12 cells are presented and discussed.

Neolamellarin A及其相关吡咯类海洋生物碱合成和结构改造研究进展

Lamellarins是1类从海洋无脊椎动物中分离的具有生物活性的吡咯生物碱,Neolamellarins,Lukianols,Storniamides,Ningalins等结构新颖的生物碱都属于该家族。Lamellarins吡咯类生物碱合成的关键是1,3,4-三取代吡咯环的构建,主要策略有分步构建与一锅法构建吡咯环两类,从中涌现了多种极富创新性与可行性的合成方法,既从结构多样性合成的角度丰富了化合物库,同时又以生物活性为导向提高了该类化合物的生物活性。本文对其结构特点、合成、生物活性进行了综述。

海洋来源Neolamellarin A类似物的神经保护活性

目的生物碱是自然界中普遍存在的一类含氮的碱性有机化合物,其中海洋生物碱因具有广泛的生物活性而受到极大关注。Neolamellarin A是1种来源于海洋动物海绵并具有新颖吡咯类骨架的生物碱。目前对Neolamellarin A类生物碱的研究探索刚刚起步,希望可以通过更多的活性研究对其加以全面的开发。方法采用细胞毒活性检测(MTT法)及神经细胞保护模型对五个新颖Neolamellarin A的3,4二芳基取代全甲基化类似物进行检测。结果发现该类3,4二芳基取代全甲基化的Neolamellarin A类似物较弱的细胞毒活性和突出的神经保护活性。结论实验结果扩展了该类Neolamellarin A类似物潜在的应用方向并丰富了海洋生物碱的生物功能。

海洋来源的Lamellarin O及其类似的吡咯类生物碱的研究进展

Lamellarins以及结构相似的吡咯类生物碱是一类来源于海洋的具有新颖化学结构和潜在生物活性的生物碱,其中Lamellarin O及其相类似的生物碱都具有3,4-相同二芳基取代的吡咯母核,且它们的全甲基化衍生物具有良好的多药耐药抑制活性。该文章主要综述了Lamellarin O及其相类似的生物碱的发现、全合成、生物活性及结构改造方面的研究。