(1''R,2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-(2'-methylbutyryl)amino]octanoic acid (1''-benzylsulfanylmethylallyl)amide | 619328-42-6

• 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: (1''R,2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-(2'-methylbutyryl)amino]octanoic acid (1''-benzylsulfanylmethylallyl)amide
• 英文别名: (3R,4S,6S)-N-((R)-1-(benzylthio)but-3-en-2-yl)-8-((R)-N,2-dimethylbutanamido)-3,4,6-trimethyloctanamide；(3R,4S,6S)-N-[(2R)-1-benzylsulfanylbut-3-en-2-yl]-3,4,6-trimethyl-8-[methyl-[(2R)-2-methylbutanoyl]amino]octanamide
• CAS: 619328-42-6
• 化学式: C₂₈H₄₆N₂O₂S
• 分子量: 474.751
• InChiKey: SKKFCGXRNBZFPS-HROMDODWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  33
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1''R,2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-(2'-methylbutyryl)amino]octanoic acid (1''-benzylsulfanylmethylallyl)amide 在 氨 、 sodium 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以86%的产率得到(1''R,2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-(2'-methylbutyryl)amino]octanoic acid (1''-mercaptomethylallyl)amide
  参考文献：
  名称：

  Total synthesis of (+)-kalkitoxinElectronic supplementary information (ESI) available: experimental procedures and spectroscopic data. See http://www.rsc.org/suppdata/cc/b3/b306124h/

  摘要：

  神经毒素脂肽 (+)-kalkitoxin 的合成使用了不对称有机铜共轭加成的方法，随后通过原位烯醇盐烷基化来建立毒素的反反-1,2,4-三甲基关系；kalkitoxin 的合成总共需要十六个步骤，最终的总体产率为3%。

  DOI：

  10.1039/b306124h
• 作为产物：
  描述：

  Boc-S-苄基-L-半光氨酸 在 双(三甲基硅烷基)氨基钾 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 25.75h， 生成 (1''R,2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-(2'-methylbutyryl)amino]octanoic acid (1''-benzylsulfanylmethylallyl)amide
  参考文献：
  名称：

  + -kalkitoxin的全合成和生物学评估，这是蓝藻Lyngbya majuscula的一种细胞毒性代谢产物。

  摘要：

  由（R）-2-甲基丁酸，（R）-半胱氨酸和（3S，4S，6S）-3,4,6-三甲基-8- （甲基氨基）辛酸。合成中的关键步骤是通过将有机铜物种串联不对称共轭加成到α，β-不饱和N-酰基恶唑烷-2--2-上，然后原位通过α-甲基化来安装抗，反甲基立体三联体。产生的烯醇。烷基毒素的噻唑啉部分是通过四氯化钛催化的乙烯基取代的酰胺基硫醇的环化反应组装的。

  DOI：

  10.1039/b404205k

文献信息

• Toward Ideality: The Synthesis of (+)-Kalkitoxin and (+)-Hydroxyphthioceranic Acid by Assembly-Line Synthesis
  作者：Sebastien Balieu、Gayle E. Hallett、Matthew Burns、Teerawut Bootwicha、John Studley、Varinder K. Aggarwal

  DOI：10.1021/ja512875g

  日期：2015.4.8

  The iterative homologation of boronic esters using chiral lithiated benzoate esters and chloromethyllithium has been applied to the highly efficient syntheses of two natural products, (+)-kalkitoxin and (+)-hydroxyphthioceranic acid. The chiral lithiated benzoate esters (>99% ee) were generated from the corresponding stannanes, which themselves were prepared by HoppeBeak deprotonation of ethyl 2,4,6-triisopropyl-benzoate with s-BuLi in the presence of (+)- or (-)-sparteine and trapping with Me3SnCl followed by recrystallization. In addition, it was found that purification between several homologations could be avoided, substantially increasing both chemical and manpower efficiency. In the case of (+)-kalkitoxin, six iterative homologations were conducted on commercially available p-MeOC(6)H(4)CH(2)Bpin to build up the core of the molecule before the C-B bond was converted into the desired CN bond, without purification of intermediates. In the case of (+)-hydroxyphthioceranic acid, 16 iterative homologations were conducted on p-MeOC(6)H(4)Bpin with only four intermediate purifications before oxidation of the C-B bond to the desired alcohol. The stereocontrolled and efficient syntheses of these complex molecules highlight the power of iterative chemical synthesis using boronic esters.