(2S,3S,8S,9S,4E,6E)-3-(tert-butoxycarbonyl)amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid methyl ester | 134440-91-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2S,3S,8S,9S,4E,6E)-3-(tert-butoxycarbonyl)amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid methyl ester
• 英文别名: N-Boc 4E,6E-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid methyl ester；Boc-Adda-OMe；(2S,3S,8S,9S)-methyl-3-tert-butoxycarbonylamino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoate；methyl (2S,3S,4E,6E,8S,9S)-9-methoxy-2,6,8-trimethyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]-10-phenyldeca-4,6-dienoate
• CAS: 134440-91-8
• 化学式: C₂₆H₃₉NO₅
• 分子量: 445.599
• InChiKey: QKMOLGPCJHVBOW-KJWWZGEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3S,8S,9S,4E,6E)-3-(tert-butoxycarbonyl)amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid methyl ester 在 2,3,5-三甲基吡啶 、 lithium hydroxide 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 锌 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 93.0h， 生成 methyl (2R,3S)-2-[[(2S)-2-[[(2R)-2-[2-[[(4R)-5-methoxy-4-[[(2S,3S,4E,6E,8S,9S)-9-methoxy-2,6,8-trimethyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]-10-phenyldeca-4,6-dienoyl]amino]-5-oxopentanoyl]-methylamino]prop-2-enoylamino]propanoyl]amino]-4-methylpentanoyl]amino]-3-methyl-4-oxo-4-[[(2S)-1-oxo-1-(2,3,4,5,6-pentafluorophenoxy)propan-2-yl]amino]butanoate
  参考文献：
  名称：

  丝氨酸-苏氨酸磷酸酶抑制剂微囊藻毒素-LA的全合成

  摘要：

  由激酶和磷酸酶介导的可逆蛋白磷酸化是细胞的主要控制元件。有多种有毒的天然产物会抑制某些磷酸酶，从而破坏正常的生化途径。这些毒素可用于剖析与这些酶中的每一种相关的个体生化途径。本文描述了一种此类毒素的首次全合成，即环状七肽微囊藻毒素-LA。该合成具有收敛路线，可用于寻找选择性磷酸酶抑制剂的类似物制备。描述了一种不寻常的氨基酸 Adda 的新途径，它通过 Suzuki 偶联反应结合了有效的非对映选择性天冬氨酸烷基化和二烯合成。

  DOI：

  10.1021/ja961683e
• 作为产物：
  描述：

  methyl (2S,3R)-3-(N-Boc-amino)-4-(tert-butyldimethylsilyloxy)-2-methyl-butanoate 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 草酰氯 、 碘 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 24.83h， 生成 (2S,3S,8S,9S,4E,6E)-3-(tert-butoxycarbonyl)amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid methyl ester
  参考文献：
  名称：

  Total Synthesis of Motuporin and 5-[l-Ala]-Motuporin

  摘要：

  Total synthesis of the cyclic peptide hepatotoxin motuporin is described, including an efficient synthesis of the constituent amino acid Adda. Three strategies to motuporin are outlined with their relative strengths and weaknesses. Cyclization of the linear peptide precursor was found to proceed moderately well for peptides containing the N-methyldehydrobutyrine residue masked as a threonine, but significant C-terminal epimerization occurred in the presence of the dehydroamino acid. Replacement of the N-methyldehydrobutyrine residue by L-alanine was explored to assess the contribution of this dehydroamino acid to the biochemical activity of motuporin. Some epimerization also was observed during cyclization of the alanine-containing peptide. Synthetic motuporin and both isomers of 5-[L-Ala]-motuporin inhibit the activity of protein phosphatase-l (PP1) in rat adipocyte lysates with comparable IC50 values. These results indicate that the N-methyldehydrobutyrine residue is not essential for PP1 inhibition.

  DOI：

  10.1021/jo982145i

文献信息

• Stereoconvergent synthesis of (2S,3S,8S,9S,4E,6E)-N-Boc-ADDA starting from (S)-serine and (S)-phenyllactic acid
  作者：Fabiana D'Aniello、André Mann、Angèle Schoenfelder、Maurizio Taddei

  DOI：10.1016/s0040-4020(96)01056-3

  日期：1997.1

  β-amino acid N-Boc-ADDA is prepared following a disconnection of the CC bond between the two E,E double bonds. The stereochemistry of the two synthons was controlled using the alkylation of chiral bromoallenes derived from naturally occurring (S)-serine and (S)-phenyllactic acid. The cupration of bromoallenes derived from (S)-serine also provides a general method for the synthesis of chiral β-alkylated

  重要的天然β-氨基酸N-Boc-ADDA是在两个E，E双键之间的CC键断开后制备的。使用衍生自天然存在的（S）-丝氨酸和（S）-苯基乳酸的手性溴代烯烷基化来控制两个合成子的立体化学。衍生自（S）-丝氨酸的溴丙二烯的铜化也提供了合成手性β-烷基化的天冬氨酸衍生物的通用方法。
• Stereocontrolled synthesis of (2S, 3S, 8S, 9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4E,6E-dienoic acid (ADDA), the characteristic amino acid of microcystins and nodularin
  作者：Mark F. Beatty、Clive Jennings-White、Mitchell A. Avery

  DOI：10.1039/c39910000351

  日期：——

  (4R,5S)-4-Methyl-5-phenyloxazolidin-2-one was used as a chiral template to construct the 8S and 9S chiral centres of (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (ADDA), the 2S and 3S centres were derived from D-aspartic acid.

  以（4 R，5 S）-4-甲基-5-苯基恶唑烷丁-2-酮为手性模板，构建（2 S，3 S，8 S，9 S）-的8 S和9 S手性中心。3-氨基-9-甲氧基-2,6,8-三甲基-10-苯基癸-4,6-二烯酸（ADDA）的2 S和3 S中心衍生自D-天门冬氨酸。
• Stereocontrolled synthesis of (2S,3S,8S,9S,4E,6E)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda), the amino acid characteristic of microcystins and nodularin
  作者：Vlark F. Beatty、Clive Jennings-White、Mitchell A. Avery

  DOI：10.1039/p19920001637

  日期：——

  (4R,5S)-4-Methyl-5-phenyloxazolindin-2-one has been used as a chiral template to construct the 8S and 9S chiral centres of (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda), the 2S and 3S centres being derived from D-aspartic acid.

  （4 R，5 S）-4-甲基-5-苯基恶唑啉丁-2-一已被用作手性模板来构建（2 S，3 S，8 S，9 S）的8 S和9 S手性中心-3-氨基-9-甲氧基-2,6,8-三甲基-10-苯基癸基-4,6-二烯酸（Adda），其2 S和3 S中心衍生自D-天门冬氨酸。
• Congener-Independent Immunoassay for Microcystins and Nodularins
  作者：Werner J. Fischer、Ian Garthwaite、Christopher O. Miles、Kathryn M. Ross、James B. Aggen、A. Richard Chamberlin、Neale R. Towers、Daniel R. Dietrich

  DOI：10.1021/es011182f

  日期：2001.12.1

  microcystin (MC) heptapeptides (>60 congeners) and the nodularin pentapeptides (ca. 5 congeners). Cyanobacterial cyclic peptide toxins are harmful to man, other mammals, birds, and fish. Acute exposure to high concentrations of these toxins causes liver damage, while subchronic or chronic exposure may promote liver tumor formation. The detection of cyclic peptide cyanobacterial toxins in surface and drinking

  在全球淡水和微咸水中发现了能够产生毒性肽的蓝细菌（蓝藻）（例如微囊藻和结节藻属）。这些毒素包括微囊藻毒素（MC）七肽（> 60个同类物）和结节蛋白五肽（约5个同类物）。蓝细菌环肽毒素对人类，其他哺乳动物，鸟类和鱼类有害。急性暴露于高浓度这些毒素会导致肝损害，而亚慢性或慢性暴露可能会促进肝肿瘤的形成。由于所需的检测限低，阻碍了地表水和饮用水中环肽蓝细菌毒素的检测，并且目前的常规检测仅限于少数同类物。不寻常的β-氨基酸ADDA（4E，6E-3-氨基-9-甲氧基-2,6,8-三甲基-10-苯基癸4 大多数已知（> 80％）有毒的五肽和七肽毒素同类物中都含有6-二烯酸。在这里，我们报告了两个ADDA半抗原的合成，对ADDA的抗体的升高以及竞争性间接ELISA的发展，用于利用这些抗体检测微囊藻毒素和结节蛋白。该方法的定量限为0.02-0.07 ng / mL（取决于存在的同系物），低于WHO提出的饮用水准则（1
• A new stereoselective route to (2S, 3S, 8S, 9S, 4E, 6E)-3-amino-9-methoxy-2, 6, 8-trimethyl-10-phenyldeca-4, 6-dienoic acid (Adda)
  作者：Hong Yong Kim、Peter L. Toogood

  DOI：10.1016/0040-4039(96)00282-1

  日期：1996.4

  N-Boc-Adda has been prepared in 15 steps and 9% overall yield from the readily available alcohol, 3-pentyne-2-ol, employing a route that includes two Claisen rearrangements.

  使用包括两个克莱森重排的途径，由15种步骤制备N -Boc-Adda，总产率为9％，由现成的醇3-pentyne-2-ol制备。