brevetoxin A | 98112-41-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 短裸甲藻毒素及其衍生物
• 英文名称: brevetoxin A
• 英文别名: PbTx-1；2-[[(1S,3R,4S,6S,8R,10R,12S,16R,18S,20R,22S,24Z,27R,29S,33R,35S,37R,39R,41S,42S,44R,46S,48R,49Z)-41-hydroxy-4,8,10,46-tetramethyl-14-oxo-2,7,13,17,21,28,34,38,43,47-decaoxadecacyclo[25.24.0.03,22.06,20.08,18.012,16.029,48.033,46.035,44.037,42]henpentaconta-24,49-dien-39-yl]methyl]prop-2-enal
• CAS: 98112-41-5
• 化学式: C₄₉H₇₀O₁₃
• 分子量: 867.087
• InChiKey: MGVIMUPHKPHTKF-HQUFVKSZSA-N

物化性质

• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  62
• 可旋转键数：
  3
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  brevetoxin A 生成 (1S,3R,4S,6S,8R,10R,12S,16R,18S,20R,22S,24Z,27R,29S,33R,35S,37R,39R,41S,42S,44R,46S,48R,49Z)-41-hydroxy-39-[2-(hydroxymethyl)prop-2-enyl]-4,8,10,46-tetramethyl-2,7,13,17,21,28,34,38,43,47-decaoxadecacyclo[25.24.0.03,22.06,20.08,18.012,16.029,48.033,46.035,44.037,42]henpentaconta-24,49-dien-14-one
  参考文献：
  名称：

  BADEN, DANIEL G.;MENDE, THOMAS J.;TRAINER, VERA L., MYCOTOXINS AND PHYCOTOXINS88: COLLECT INVIT. PAP. 7TH INT. IUPAC SYMP., T+

  摘要：

  DOI：
• 作为产物：
  描述：

  N,N-二甲基氯烯亚胺 、 3-[(1S,3R,4S,6S,8R,10R,12S,16R,18S,20R,22S,24Z,27R,29S,33R,35S,37R,39R,41S,42S,44R,46S,48R,49Z)-41-hydroxy-4,8,10,46-tetramethyl-14-oxo-2,7,13,17,21,28,34,38,43,47-decaoxadecacyclo[25.24.0.03,22.06,20.08,18.012,16.029,48.033,46.035,44.037,42]henpentaconta-24,49-dien-39-yl]propanal 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以2.2 mg的产率得到brevetoxin A
  参考文献：
  名称：

  Brevetoxin A 的全合成

  摘要：

  报道了短杆菌毒素 A 的全合成。由先前报道的高级片段制备的两个四环偶联伙伴通过 Horner-Wittig 烯化有效地结合在一起。所得的八环被发展为用于还原醚化的底物，其成功导致了倒数第二个四醇中间体。四醇通过快速的选择性氧化过程转化为天然产物，然后进行亚甲基化。

  DOI：

  10.1021/ol802710u

文献信息

• Solution Reactivity of Brevetoxins As Monitored by Electrospray Ionization Mass Spectrometry and Implications for Detoxification
  作者：Yousheng Hua、Richard B. Cole

  DOI：10.1021/tx9900876

  日期：1999.12.1

  brevetoxin compounds in acid and base and under oxidizing conditions were studied using electrospray ionization mass spectrometry (ESI-MS) to monitor reaction products. Brevetoxins are determined to be unstable in acidic and basic solutions. Under acidic conditions, brevetoxins containing an aldehyde functional group in the terminal "tail" side chain are easily converted to acetal structures, while "head"

  使用电喷雾电离质谱（ESI-MS）监测反应产物，研究了短毒素在酸，碱和氧化条件下的反应性。经测定，布雷维毒素在酸性和碱性溶液中不稳定。在酸性条件下，末端“尾部”侧链中含有醛基官能团的短毒素容易转化为缩醛结构，而“头部”侧内酯开环的过程更缓慢。反应速率常数的测量表明在酸性条件下的反应性如下顺序：Btx-1> Btx-2> Btx-9。在碱性条件下，氢氧根离子在头部的侵蚀会导致内酯环打开。对于Btx-2和Btx-9，碱水解（在50:50甲醇/水中的0.01 N NaOH）在120分钟内完成，但是Btx-1对完成没有反应。酸水解和碱水解均可导致可逆的内酯开环，但在可比条件下，碱水解比酸水解进行得更快。酸处理不是使短毒素解毒的有效方法。碱处理可以打开内酯环（B型短毒素比A型短毒素进行得更快），导致生成的产品据说无毒，但反应是可逆的。牛vet毒素显示出不可逆且相对较快的反应容易被高锰酸盐氧化的可能，
• Structure of brevetoxin A (GB-1 toxin), the most potent toxin in the Florida red tide organism Gymnodinium breve (Ptychodiscus brevis)
  作者：Yuzuru. Shimizu、Hong Nong. Chou、Hideo. Bando、Gregory. Van Duyne、Jon. Clardy

  DOI：10.1021/ja00263a031

  日期：1986.2

  the following electronic spectrum: A, , cyclohexane 218 (c 8900) and 318 (3000). Photoelectron spectroscopic measurements on 1 will be reported elsewhere. Heating a CDC13 solution of 1 to 80 O C induces clean rearrangement to 1618 ( t l -7 h). The same isomerization can be achieved more rapicily by irradiation with a TLC UV lamp (A 254 nm). Accordingly, 1 finds [1,3] sigmatropic migration to be most accessible

  用 NBS 溴化，用锌铜对、碘化钾和 DMF 中的碘 (24%) 进行脱溴。69i6 同样，C，从 NMR 光谱中可以明显看出对称性。” 无色结晶物质 (mp 27-29 "C)显示以下电子光谱：A, , 环己烷 218 (c 8900) 和 318 (3000)。1 上的光电子光谱测量将在别处报道。加热 1 至 80 OC 的 CDC13 溶液会导致清洁重排至 1618 (tl -7 h)。通过用 TLC 紫外灯 (A 254 nm) 照射，可以更快速地实现相同的异构化。因此，1 发现 [1,3] σ 迁移最容易从其基态和激发态获得。
• Total Synthesis of Brevetoxin A: Part 4: Final Stages and Completion
  作者：K. C. Nicolaou、Janet L. Gunzner、Guo-qiang Shi、Konstantinos A. Agrios、Peter Gärtner、Zhen Yang

  DOI：10.1002/(sici)1521-3765(19990201)5:2<646::aid-chem646>3.0.co;2-e

  日期：1999.2.1

  The total synthesis of brevetoxin A is described, Our methodology of palladium-catalyzed couplings with cyclic ketene acetal phosphates was utilized to functionalize nine-membered ring lactone 4 followed by a [4+2] singlet oxygen addition to the resulting 1,3-diene (6), The product endoperoxide (7) was transformed into coupling partners 3a and 3b to be reacted with aldehyde 2, Our first attempted union of 3a and aldehyde 2 failed, most probably due to steric hindrance, which led us to explore other olefination coupling reactions. Horner- Wittig type coupling was found to be successful on advanced model systems: diphenylphosphine oxides 21 and 28 were each coupled with aldehyde 2. Key intermediates 3b and 2 were successfully coupled and ring F oxocene (44) was cyclized through the hydroxy dithioketal cyclization methodology, The final manipulations were then executed to complete the first total synthesis of brevetoxin A.