sipholenol A | 78518-73-7

• 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: sipholenol A
• 英文别名: (3S,5As,6S,7R,9aS)-6-[2-[(1S,3aS,5R,8aS)-1-hydroxy-1,4,4,6-tetramethyl-2,3,3a,5,8,8a-hexahydroazulen-5-yl]ethyl]-2,2,5a,7-tetramethyl-4,5,6,8,9,9a-hexahydro-3H-benzo[b]oxepine-3,7-diol
• CAS: 78518-73-7
• 化学式: C₃₀H₅₂O₄
• 分子量: 476.74
• InChiKey: LVWWPNAIMBYRKG-RSNOKGJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  69.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  sipholenol A 在 4-二甲氨基吡啶 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 3.0h， 生成 4-[[(3S,5aS,6S,7R,9aS)-6-[2-[(3aS,5R,8aS)-1,4,4,6-tetramethyl-3a,5,8,8a-tetrahydro-3H-azulen-5-yl]ethyl]-7-hydroxy-2,2,5a,7-tetramethyl-4,5,6,8,9,9a-hexahydro-3H-benzo[b]oxepin-3-yl]oxy]-4-oxobutanoic acid
  参考文献：
  名称：

  海洋三萜硅油酚作为乳腺癌迁移和侵袭抑制剂的优化。

  摘要：

  从红海海绵Callyspongia siphonella分离出的七氟烷三萜烯Sipholenol A能够逆转过度表达P-糖蛋白（P-gp）的癌细胞的多药耐药性。在这里，据报道，在伤口愈合试验中，西佛洛酚A和类似物对高度转移的人乳腺癌细胞MDA-MB-231细胞具有抗迁移活性。使用基于配体的策略半合成优化了西佛来酚A和西佛来酮A，以生成结构多样的类似物，以最大程度地发挥其抗迁移活性。通过广泛的一维和二维NMR光谱学和高分辨率质谱分析，总共生成并鉴定了22种半合成酯，醚，肟和氨基甲酸酯类似物。在IC伤口愈合试验中，Sipholenol A4β-4-氯苯甲酸酯和19,20-脱水Sipholenol A4β-4-氯苯甲酸酯是所有测试的类似物中最有效的类似物。50个的值5.3和5.9μ中号分别。通常，酯衍生物显示出比氨基甲酸酯类似物更好的抗迁移活性。KINOME扫描针对451种人类蛋白激酶的19,2

  DOI：

  10.1002/cmdc.201200516

文献信息

• Optimization, pharmacophore modeling and 3D-QSAR studies of sipholanes as breast cancer migration and proliferation inhibitors
  作者：Ahmed I. Foudah、Asmaa A. Sallam、Mohamed R. Akl、Khalid A. El Sayed

  DOI：10.1016/j.ejmech.2013.11.039

  日期：2014.2

  evidence for future design of novel antimigratory compounds based on a simplified sipholane structure possessing rings A and B (perhydrobenzoxepine) connected to substituted aromatic esters, with the elimination of rings C and D ([5,3,0]bicyclodecane system). This will enable the future synthesis of the new active entities feasibly and cost-effectively. These results demonstrate the potential of marine

  从红海海绵Callyspongia siphonella中分离出的三萜烯Sipholenol A先前已显示出可以逆转过表达P-糖蛋白的癌细胞的多药耐药性。此外，西番莲显示出对转移的人乳腺癌细胞系MDA-MB-231的侵袭和迁移有希望的体外抑制作用。乳腺癌肿瘤激酶（Brk）是癌细胞表型的介导因子，对增殖，存活和迁移很重要，被认为是潜在的靶标。这项研究报告了西佛来酚A酯的其他半合成优化，以改善乳腺癌的抗迁移和抗增殖活性以及Brk磷酸化抑制作用。十五种新的西佛洛尔A类似物（25 – 39）进行半合成。西佛烯酚A4β-4'，5'-二氯苯甲酸酯（29）最有效，在迁移分析中IC 50值为1.3μM 。使用Z'-LYTE™激酶测定和Western印迹分析评估了29的Brk磷酸化抑制水平。活性类似物以等于其IC 50的剂量对非致瘤性上皮性乳腺癌细胞MCF10A无毒性在迁移和增殖分析中的值等于或高于此值，表
• Biocatalysis of the Anticancer Sipholane Triterpenoids
  作者：Sandeep Jain、Amit Shirode、Shenouda Yacoub、Ashley Barbo、Paul Sylvester、Eric Huntimer、Fathi Halaweish、Khalid El Sayed

  DOI：10.1055/s-2007-967188

  日期：2007.6

  The Red Sea sponge Callyspongia (= Siphonochalina) siphonella is a rich source of sipholane triterpenoids. Biocatalysis of the major sipholanes, sipholenol A (1) and sipholenone A (2), respectively, by Mucor ramannianus ATCC 9628 and Cunninghamella elegans ATCC 7929 afforded four new metabolites 3 - 6 along with sipholenol G and 28-hydroxysipholenol A. Major sipholanes along with their biocatalytic products were investigated for their antiproliferative activity against the highly malignant +SA mouse mammary epithelial cell line. Sipholenone A (2) was the most active sipholane inhibiting +SA cell proliferation with an IC50 value of 20 - 30 μM. Sipholenone A, also, showed cytotoxicity against MCF-7 at a dose of 0.9 μM and antiangiogenic activity in the CAM (chorio-allantoic membrane) assay. This is the first report on anticancer activity of these triterpenoids.

  红海海绵 Callyspongia (= Siphonochalina) siphonella 是ipholane 三萜类化合物的丰富来源。Mucor ramannianus ATCC 9628 和 Cunninghamella elegans ATCC 7929 分别对主要的鞘氨醇--鞘氨醇 A（1）和鞘氨醇酮 A（2）进行生物催化，得到了四种新的代谢产物 3 - 6 以及鞘氨醇 G 和 28-hydroxysipholenol A。双酚 A（2）是抑制 +SA 细胞增殖活性最强的双酚烷，其 IC50 值为 20 - 30 μM。此外，在剂量为 0.9 ¼M 时，四氢芬酮 A 对 MCF-7 也有细胞毒性；在 CAM（绒毛膜-尿囊膜）试验中，四氢芬酮 A 还具有抗血管生成活性。这是首次报道这些三萜类化合物的抗癌活性。
• High-field FT NMR application of Mosher's method. The absolute configurations of marine terpenoids
  作者：Ikuko Ohtani、Takenori Kusumi、Yoel Kashman、Hiroshi Kakisawa

  DOI：10.1021/ja00011a006

  日期：1991.5

  Mosher's (H-1) method to elucidate the absolute configuration of secondary alcohols was reexamined by use of high-field FT NMR spectroscopy, which enables assignment of most of the protons of complex molecules. There is a systematic arrangement of DELTA-delta (delta-S - delta-R) values obtained for the (R)- and (S)-MTPA esters of (-)-menthol, (-)-borneol, cholesterol, and ergosterol, the absolute configurations of which are known. Analysis of the DELTA-delta values of these compounds led to a rule that could predict the absolute configurations of natural products. When this rule was applied to some marine terpenoids including cembranolides and xenicanes, their absolute configurations were assigned and a part of the results were confirmed by X-ray structural analyses. In the case of sipholenol A, which has a sterically hindered OH group, this rule is inapplicable. But the problem is overcome by inverting the OH group to a less sterically hindered position; the resulting epimer gives systematically arranged DELTA-delta values, which enabled the elucidation of the absolute configuration. Comparison of the present method with Mosher's F-19 method indicates that the latter one using F-19 NMR lacks in reliability.
• A new aspect of the high-field NMR application of Mosher's method. The absolute configuration of marine triterpene sipholenol A
  作者：Ikuko Ohtani、Takenori Kusumi、Yoel Kashman、Hiroshi Kakisawa

  DOI：10.1021/jo00003a067

  日期：1991.2
• Optimization of Marine Triterpene Sipholenols as Inhibitors of Breast Cancer Migration and Invasion
  作者：Ahmed I. Foudah、Sandeep Jain、Belnaser A. Busnena、Khalid A. El Sayed

  DOI：10.1002/cmdc.201200516

  日期：2013.3

  Sipholenol A, a sipholane triterpene isolated from the Red Sea sponge Callyspongia siphonella, has the ability to reverse multidrug resistance in cancer cells that overexpress P‐glycoprotein (P‐gp). Here, the antimigratory activity of sipholenol A and analogues are reported against the highly metastatic human breast cancer cell line MDA‐MB‐231 in a wound‐healing assay. Sipholenol A and sipholenone A

  从红海海绵Callyspongia siphonella分离出的七氟烷三萜烯Sipholenol A能够逆转过度表达P-糖蛋白（P-gp）的癌细胞的多药耐药性。在这里，据报道，在伤口愈合试验中，西佛洛酚A和类似物对高度转移的人乳腺癌细胞MDA-MB-231细胞具有抗迁移活性。使用基于配体的策略半合成优化了西佛来酚A和西佛来酮A，以生成结构多样的类似物，以最大程度地发挥其抗迁移活性。通过广泛的一维和二维NMR光谱学和高分辨率质谱分析，总共生成并鉴定了22种半合成酯，醚，肟和氨基甲酸酯类似物。在IC伤口愈合试验中，Sipholenol A4β-4-氯苯甲酸酯和19,20-脱水Sipholenol A4β-4-氯苯甲酸酯是所有测试的类似物中最有效的类似物。50个的值5.3和5.9μ中号分别。通常，酯衍生物显示出比氨基甲酸酯类似物更好的抗迁移活性。KINOME扫描针对451种人类蛋白激酶的19,2