(-)-8,15-diisocyano-11(20)-amphilectene

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (-)-8,15-diisocyano-11(20)-amphilectene
• 英文别名: (-)-DINCA；(1S,3aR,4S,6S,6aS,9aS,9bS)-9a-isocyano-6-(2-isocyano-2-methylpropyl)-1,4-dimethyl-7-methylidene-2,3,3a,4,5,6,6a,8,9,9b-decahydro-1H-phenalene
• 化学式: C₂₂H₃₂N₂
• 分子量: 324.509
• InChiKey: JZQFIFOTCYCVEG-XQOOQLJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  8.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-8,15-diisocyano-11(20)-amphilectene 在 selenium 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以78%的产率得到8,15-diisoselenocyano-11(20)-amphilectene
  参考文献：
  名称：

  Natural product-based synthesis of novel anti-infective isothiocyanate- and isoselenocyanate-functionalized amphilectane diterpenes

  摘要：

  来自加勒比海绵Svenzea flava的海洋天然产物(−)-8,15-二异氰酸酯-11(20)-amphilectene被用作合成五个新产物的结构骨架，所有这些产物均针对实验室菌株的恶性疟原虫（Plasmodium falciparum）和结核分枝杆菌（Mycobacterium tuberculosis H37Rv）进行了测试。该骨架包含两个易于进行化学修饰的异氰酸酯单元，使其能够被扩展成一个包含硫和硒的化合物小型库。骨架本身及其异硫氰酸酯和异硒氰酸酯类似物展现出低至次微摩尔级别的抗疟活性。

  公开号：

  US10173974B1

文献信息

• Synthesis and preliminary biological evaluation of a small library of hybrid compounds based on Ugi isocyanide multicomponent reactions with a marine natural product scaffold
  作者：Edward Avilés、Jacques Prudhomme、Karine G. Le Roch、Scott G. Franzblau、Kevin Chandrasena、Alejandro M.S. Mayer、Abimael D. Rodríguez

  DOI：10.1016/j.bmcl.2015.09.033

  日期：2015.11

  Mycobacterium tuberculosis H37Rv and chloroquine-susceptible 3D7 Plasmodium falciparum. Interestingly, compounds 4–8 displayed potent in vitro antiparasitic activity with higher cytotoxicity in comparison to their diisocyanide precursor 3, with the best compound exhibiting an IC50 value of 3.6 nM. Additionally, these natural product inspired hybrids potently inhibited in vitro thromboxane B2 (TXB2)

  基于天然的二异氰酸酯3，通过平行的Ugi四中心三组分反应（U-4C-3CR），成功地合成了五种Ugi加合物（基于混合物）的组合库，其中包含已知的抗结核药和抗疟药效基团（4 – 8个） 。评价了获得的新型α-酰基氨基酰胺对实验室菌株结核分枝杆菌H 37 Rv和对氯喹敏感的3D7恶性疟原虫的抗感染能力。有趣的是，化合物4 - 8显示在体外抗寄生虫活性有效的具有更高的细胞毒性相比，它们的前体diisocyanide如图3所示，最佳化合物的IC 50值为3.6 nM。此外，这些天然产物的启发体外血栓素B2有效地抑制杂种2（TXB 2）和超氧阴离子（O 2 - ）产生从大肠杆菌脂多糖（LPS）激活的大鼠新生小胶质细胞，伴随低短期毒性。
• Monamphilectine A, a Potent Antimalarial β-Lactam from Marine Sponge <i>Hymeniacidon</i> sp: Isolation, Structure, Semisynthesis, and Bioactivity
  作者：Edward Avilés、Abimael D. Rodríguez

  DOI：10.1021/ol102351z

  日期：2010.11.19

  Monamphilectine A (1), a new diterpenoid β-lactam alkaloid showing potent antimalarial activity, was isolated in milligram quantities following bioassay-directed extraction of a Puerto Rican marine sponge Hymeniacidon sp. Its structure, established by interpretation of spectral data, was confirmed unequivocally by chemical interconversion and comparison of physical, chemical, and bioactivity data with the natural

  Monamphilectine A ( 1 ) 是一种新的二萜类 β-内酰胺生物碱，显示出有效的抗疟活性，在对波多黎各海海绵Hymeniacidon sp. 进行生物测定指导提取后，以毫克量分离。它的结构是通过光谱数据的解释确定的，通过化学互变以及物理、化学和生物活性数据与天然产物的比较得到明确证实。monamphilectine A 的一步半合成基于多组分 Ugi 反应，该反应也建立了其绝对立体结构。
• Marine sponge Hymeniacidon sp. amphilectane metabolites potently inhibit rat brain microglia thromboxane B2 generation
  作者：Alejandro M.S. Mayer、Edward Avilés、Abimael D. Rodríguez

  DOI：10.1016/j.bmc.2011.10.086

  日期：2012.1

  The effects of five Hymeniacidon sp. amphilectane metabolites (1–5) and two semi-synthetic analogs (6 and 7) on thromboxane B2 (TXB2) and superoxide anion (O2-) generation from Escherichia coli LPS-activated rat brain microglia were investigated. All Hymeniacidon sp. metabolites and analogs potently inhibited TXB2 (IC50 = 0.20–4.69 μM) with low lactate dehydrogenase release and minimal mitochondrial

  五种Hymeniacidon sp.的影响。amphilectane代谢物（1 - 5）和两个半合成类似物（6和7血栓素B2上）2（TXB 2）和超氧阴离子（哦2——)研究了大肠杆菌LPS 激活的大鼠脑小胶质细胞的生成。所有Hymeniacidon sp。代谢物和类似物有效抑制 TXB 2 (IC 50  = 0.20–4.69 μM)，乳酸脱氢酶释放低，线粒体脱氢酶抑制最小。虽然缺乏哦2——抑制表明Hymeniacidon sp。代谢物和衍生物通过环加氧酶依赖性机制抑制 TXB 2合成，它们的药理学效力和有限的体外细胞毒性值得进一步研究，以将它们开发为先导化合物，以调节神经炎症性疾病中活化小胶质细胞增强的 TBX 2释放。
• Structural and stereochemical revision of isocyanide and isothiocyanate amphilectenes from the Caribbean marine sponge Cribochalina sp.
  作者：Maria Letizia Ciavatta、Margherita Gavagnin、Emiliano Manzo、Raffaella Puliti、Carlo Andrea Mattia、Lelio Mazzarella、Guido Cimino、Jamie S. Simpson、Mary J. Garson

  DOI：10.1016/j.tet.2005.05.102

  日期：2005.8

  The absolute stereochemistry of amphilectene metabolites from Cribochalina sp. has been revised by a detailed NMR spectroscopic study of the Mosher ester derivatives of a related alcohol. The relative stereochemistry of the previously described amphilectenes has been reinvestigated and reassigned on the basis of the X-ray structural analysis carried out on one of them. The structure of a new amphilectene

  Cribochalina sp。的两性菌素代谢物的绝对立体化学。已通过对相关醇的Mosher酯衍生物进行的详细NMR光谱研究对NMR进行了修订。基于对其中一种进行的X射线结构分析，已经对上述两亲物的相对立体化学进行了重新研究和重新分配。还介绍了一种新的两性代谢物的结构，它是一种异硫氰酸根类似物。
• Structures, semisyntheses, and absolute configurations of the antiplasmodial α-substituted β-lactam monamphilectines B and C from the sponge Svenzea flava
  作者：Edward Avilés、Jacques Prudhomme、Karine G. Le Roch、Abimael D. Rodríguez

  DOI：10.1016/j.tet.2014.11.060

  日期：2015.1

  Bioassay-guided fractionation of the Caribbean sponge Svenzea flava collected near Mona Island, off the west coast of Puerto Rico, led to the isolation of two isocyanide amphilectane-type diterpenes named monamphilectines B and C (2 and 3). Attached to the backbone of each of these compounds is the first a-substituted monocyclic beta-lactam ring to be isolated from a marine organism. The molecular structures of 2 and 3 were established by spectroscopic methods and then confirmed unequivocally by chemical correlation and comparison of physical and chemical data with the natural products. The new beta-lactams were successfully synthesized in one step, starting from the known diisocyanide 4, via parallel Ugi four-center three-component reactions (U-4C-3CR) that also established their absolute stereostructures. Interestingly, compounds 2 and 3 exhibited activities in the low nanomolar range against the human malaria parasite Plasmodium falciparum. (C) 2014 Elsevier Ltd. All rights reserved.