(2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-2'-(methylbutyryl)amino]octanoic acid | 320742-83-4

• 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: (2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-2'-(methylbutyryl)amino]octanoic acid
• 英文别名: (3R,4S,6S)-3,4,6-trimethyl-8-[methyl-[(2R)-2-methylbutanoyl]amino]octanoic acid
• CAS: 320742-83-4
• 化学式: C₁₇H₃₃NO₃
• 分子量: 299.454
• InChiKey: ANXKYZNYGSEARQ-APIJFGDWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-2'-(methylbutyryl)amino]octanoic acid 在 氨 、 sodium 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 1.08h， 生成
  参考文献：
  名称：

  Toward Ideality: The Synthesis of (+)-Kalkitoxin and (+)-Hydroxyphthioceranic Acid by Assembly-Line Synthesis

  摘要：

  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.

  DOI：

  10.1021/ja512875g
• 作为产物：
  描述：

  (4S,2'S,3'S,5'S)-3-(7'-oxo-2',3',5'-trimethylheptanoyl)-4-phenyloxazolidin-2-one 在 盐酸 、 sodium chlorite 、 sodium dihydrogenphosphate 、 锂硼氢 、 正丁基锂 、 N-羟基-7-氮杂苯并三氮唑 、 2-甲基-2-丁烯 、 草酰氯 、 sodium cyanoborohydride 、 二甲基亚砜 、 sodium sulfate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 18.91h， 生成 (2'R,3R,4S,6S)-3,4,6-trimethyl-8-[methyl-2'-(methylbutyryl)amino]octanoic acid
  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

• Total synthesis of (+)-kalkitoxinElectronic supplementary information (ESI) available: experimental procedures and spectroscopic data. See http://www.rsc.org/suppdata/cc/b3/b306124h/
  作者：James D. White、Chang-Sun Lee、Qing Xu

  DOI：10.1039/b306124h

  日期：——

  The neurotoxic lipopeptide (+)-kalkitoxin was synthesized by a route which employed asymmetric organocopper conjugate addition followed by in situ enolate alkylation to install the anti,anti-1,2,4-trimethyl relationship of the toxin; the synthesis of kalkitoxin required sixteen steps and proceeded in 3% overall yield.

  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%。
• An expeditious total synthesis of kalkitoxins: determination of the absolute stereostructure of natural kalkitoxin
  作者：Fumiaki Yokokawa、Toshinobu Asano、Tatsufumi Okino、William H. Gerwick、Takayuki Shioiri

  DOI：10.1016/j.tet.2004.06.014

  日期：2004.8

  Kalkitoxin, a potent neurotoxin isolated from the marine cyanobacteria Lyngbya majuscula, and its congeners (1–7) were efficiently synthesized utilizing Hruby's diastereoselective 1,4-addition and the Wipf's oxazoline-thiazoline conversion as key steps. These synthetic efforts in combination with spectral studies of natural kalkitoxin clearly determined the absolute stereostructure of kalkitoxin to

  Kalkitoxin，一种强效神经毒素从海洋蓝细菌分离鞘丝藻majuscula，其同类物（1 - 7）被有效地合成利用Hruby的非对映选择性1,4-加成和Wipf的恶唑啉噻唑啉转化为关键步骤。这些合成的努力与自然kalkitoxin的光谱研究相结合，明确确定kalkitoxin的绝对立体结构为7。
• Synthesis and Biological Activity of Kalkitoxin and its Analogues
  作者：Taiki Umezawa、Manabu Sueda、Takao Kamura、Teppei Kawahara、Xuerong Han、Tatsufumi Okino、Fuyuhiko Matsuda

  DOI：10.1021/jo201951s

  日期：2012.1.6

  Total syntheses of kalkitoxin, isolated from the Caribbean Lyngbya majuscula, and its analogues, 3-epi-, 7-epi-, 8-epi-, 10-epi-, 10-nor-, and 16-nor-kalldtcocin, were achieved via oxazolidinone-based diastereoselective 1,4-addition reaction of a methyl group and efficient T1C14-mediated thiazoline ring formation as the key steps. The biological activities of synthetic kalkitoxin and its analogues were evaluated with brine shrimp.
• Structure, Synthesis, and Biological Properties of Kalkitoxin, a Novel Neurotoxin from the Marine Cyanobacterium <i>Lyngbya </i><i>m</i><i>ajuscula</i>
  作者：Min Wu、Tatsufumi Okino、Lisa M. Nogle、Brian L. Marquez、R. Thomas Williamson、Namthip Sitachitta、Frederick W. Berman、Thomas F. Murray、Kevin McGough、Robert Jacobs、Kimberly Colsen、Toshinobu Asano、Fumiaki Yokokawa、Takayuki Shioiri、William H. Gerwick

  DOI：10.1021/ja005526y

  日期：2000.12.1
• Total synthesis and biological evaluation of (+)-kalkitoxin, a cytotoxic metabolite of the cyanobacterium Lyngbya majusculaElectronic supplementary information (ESI) available: 1H NMR spectrum of synthetic (+)-kalkitoxin in C6D6. See http://www.rsc.org/suppdata/ob/b4/b404205k/
  作者：James D. White、Qing Xu、Chang-Sun Lee、Frederick A. Valeriote

  DOI：10.1039/b404205k

  日期：——

  +-Kalkitoxin, a metabolite of the marine cyanobacterium Lyngbya majuscula, was synthesized from (R)-2-methylbutyric acid, (R)-cysteine, and (3S, 4S, 6S)-3,4,6-trimethyl-8-(methylamino)octanoic acid. A key step in the synthesis was installation of the anti,anti methyl stereotriad by means of a tandem asymmetric conjugate addition of an organocopper species to an alpha,beta-unsaturated N-acyl oxazolidin-2-one

  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。