(S)-(2E)-4-methylhex-2-enoic acid | 82166-24-3

• 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: (S)-(2E)-4-methylhex-2-enoic acid
• 英文别名: (2E,4S)-4-methylhex-2-enoic acid；(4S)-2E-4-methylhex-2-enoic acid；(S)-(E)-4-methylhex-2-enoic acid；(4S,E)-4-methylhex-2-enoic acid；(4s,2e)-4-Methylhex-2-enoic acid；(E,4S)-4-methylhex-2-enoic acid
• CAS: 82166-24-3
• 化学式: C₇H₁₂O₂
• 分子量: 128.171
• InChiKey: QDYRHGGXBLRFHS-OVCGOVNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-(2E)-4-methylhex-2-enoic acid 在 氢气 作用下， 生成 (4S)-4-甲基-己酸
  参考文献：
  名称：

  淡紫色拟青霉A-267的新型肽类抗生素亮氨酸抑素A的结构

  摘要：

  从淡紫色拟青霉A-267的培养滤液中分离出一种新的抗生素亮氨酸抑素A，并通过质谱和降解法对其结构进行了阐明。

  DOI：

  10.1039/c39820000094
• 作为产物：
  描述：

  (S)-2-甲基丁醛 在 氢氧化钾 、 sodium hydride 作用下， 以 乙二醇二甲醚 为溶剂， 生成 (S)-(2E)-4-methylhex-2-enoic acid
  参考文献：
  名称：

  亮氨酸他汀类药物的（2S，4S，6S）-2-氨基-6-羟基-4-甲基-8氧代鸟酸和（4S，E）-4-甲基己基-2-烯酸的合成

  摘要：

  描述了肽抗生素亮抑素的两种非天然酸和氨基酸组成的合成。

  DOI：

  10.1016/0040-4039(91)80606-7

文献信息

• Structure-activity relationship study of leucinostatin A, a modulator of tumor−stroma interaction
  作者：Hikaru Abe、Manabu Kawada、Chiharu Sakashita、Takumi Watanabe、Masakatsu Shibasaki

  DOI：10.1016/j.tet.2018.05.064

  日期：2018.9

  was performed to gain insight into the structural requirements for leucinostatin A to exhibit antiproliferative activity against DU-145 prostate cancer cells under cocultured conditions with the corresponding stromal cells. Twenty truncated peptide analogs of leucinostatin A revealed that the nonapeptide structure as a whole is essential for the biological activity. Alanine scanning demonstrated the importance

  进行了亮氨酸抑素A（一种天然的九肽）的结构-活性关系研究，以了解亮氨酸抑素A在与相应基质细胞共培养的条件下对DU-145前列腺癌细胞具有抗增殖活性的结构要求。亮氨酸抑素A的二十个截短的肽类似物表明，整个非肽结构对于生物学活性是必不可少的。丙氨酸扫描证明了某些氨基酸成分的重要性，包括羟胺和来自N末端的第二个亮氨酸。三种氨基异丁酸中的两种可以被丙氨酸的对映异构体之一取代，这清楚地表明，这些部分中的每个甲基基团均对生长抑制活性具有独特的影响。
• Three new azaphilones produced by a marine fish-derived chaetomium globosum
  作者：Takeshi Yamada、Masaaki Jinno、Takashi Kikuchi、Tetsuya Kajimoto、Atsushi Numata、Reiko Tanaka

  DOI：10.1038/ja.2012.40

  日期：2012.8

  were isolated from a strain of Chaetomium globosum originally obtained from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated based on the basis of spectroscopic analyses, including 1D and 2D NMR techniques and some chemical transformations. Particularly, chaetomugilins T and U are the first compounds without a chlorine atom in azaphilones isolated from this fungal strain

  从最初从海水鱼Mugil cephalus的球壳拟杆菌（Chaetomium globosum）菌株中分离出了三种新的代谢产物，即chaetomugilin S，dechloro-chaetomugilin D和dechloro-chaetomugilin D，并基于光谱分析，包括1D，阐明了它们的绝对立体结构。和2D NMR技术以及一些化学转化。特别地，迄今为止，脂粘蛋白T和U是在从该真菌菌株分离的氮杂苯甲酮中首先没有氯原子的化合物。此外，这些化合物适度抑制了培养的P388，HL-60，L1210和KB细胞系的生长。
• New Glutamine-Containing Azaphilone Alkaloids from Deep-Sea-Derived Fungus Chaetomium globosum HDN151398
  作者：Chunxiao Sun、Xueping Ge、Shah Mudassir、Luning Zhou、Guihong Yu、Qian Che、Guojian Zhang、Jixing Peng、Qianqun Gu、Tianjiao Zhu、Dehai Li

  DOI：10.3390/md17050253

  日期：——

  Three new azaphilone alkaloids containing glutamine residues, namely N-glutarylchaetoviridins A-C (1-3), together with two related compounds (4 and 5) were isolated from the extract of Chaetomium globosum HDN151398, a fungus isolated from a deep-sea sediment sample collected in South China Sea. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as HRESIMS spectroscopic

  从球壳龟HDN151398的提取物中分离出三种含有谷氨酰胺残基的新的氮杂酮生物碱，即N-谷氨酰chaetoviridins AC（1-3），以及两种相关的化合物（4和5），这是一种从深海沉积物样品中分离出的真菌在南海。在广泛的1D和2D NMR以及HRESIMS光谱数据和化学分析的基础上阐明了它们的结构。N-谷氨酰chaetoviridins AC（1-3）代表第一类chaetoviridins，其特征在于嵌入的谷氨酸残基。氨基酸温育实验产生了5个载有氮杂苯甲酮的不同氨基酸残基（6-10），这表明该方法可以通过与氨基酸一起培养来增强该菌株的结构多样性。
• ANTIPROTOZOAL COMPOUNDS
  申请人：Bacoba AG

  公开号：EP3345917A1

  公开（公告）日：2018-07-11

  The present invention relates to a compound of formula (I) wherein --A-- represents a peptide chain, wherein said peptide chain consists of 5 to 7 amino acids, wherein said amino acids are selected from any amino acid, wherein at least two, preferably at least three of said 5 to 7 amino acids are α-aminoisobutyric acid (Aib), leucine (Leu) or alanine (Ala); R1 is wherein X is N or CH; R5 is selected from H, C1-C16alkyl, C1-C16alkenyl, C(O)-C1-C16alkyl, C(O)-C1-C16alkenyl, (wherein said C1-C16alkyl, C1-C16alkenyl, C(O)-C1-C16alkyl, C(O)-C1-C16alkenyl are) independently optionally substituted with halogen, NR11R12, -[O-C2H4]n-OCH3 wherein n=2-20; C(O)-R8, C(O)-C1-C3alkylene-R8, N(H)C(O)-R8, or S(O)2-R9, wherein R8 is independently at each occurrence selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C1-C4alkyl, halogen, CF3, OR10, NR11R12, C6H5 and C6H5 substituted with halogen, C1-C3alkyl, OR10, NR11R12; wherein R10, R11, R12 are independently at each occurrence H, C1-C3alkyl; R9 is independently at each occurrence selected from C1-C4alkyl, aryl, heteroaryl, each independently optionally substituted with C1-C4alkyl, halogen, CF3, OR13, NR14R15; wherein R13, R14, R15 are independently at each occurrence H, C1-C3alkyl; R6, R7 are independently at each occurrence selected from H, C1-C4alkyl, C1-C4alkenyl, C(O)-C1-C3alkyl, C(O)-C1-C4alkenyl, (wherein said C1-C4alkyl, C1-C4alkenyl, C(O)-C1-C3alkyl, C(O)-C1-C4alkenyl are) independently optionally substituted with halogen, NR11R12; or R6 and R7 together with the X-C to which they are attached form independently at each occurrence an aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally (further) substituted with C1-C4alkyl, halogen, CF3, OR10, NR11R12, C6H5 and C6H5 substituted with halogen, C1-C3alkyl, OR10, NR11R12; wherein R10, R11, R12 are independently at each occurrence H, C1-C3alkyl; and wherein the arrow indicates the attachment to the NH-moiety depicted in formula (I); R2 is selected from C1-C14alkyl, C2-C14alkyl optionally substituted with OH, C2-C14alkoxy, C2-C14alkenyl optionally substituted with OH; C1-C8alkylene-R23, wherein in alkylene one or two -CH2- moieties are optionally replaced by -CH(NR24R25)-,-CH(OH)-, -C(=O)-, -NR24R25- or -CH(CH3)- moieties, wherein there are no adjacent-C(=O)- moieties or adjacent -NR24R25- moieties, and wherein R23 is independently at each occurrence selected from hydrogen; aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C1-C4alkyl, OR26, NR27R28; wherein R26, R27, R28 are independently at each occurrence H, halogen, CF3, C1-C3alkyl; and wherein R24 and R25 are independently at each occurrence H, C1-C3alkyl; with the proviso that R2 is not -CH2CH(CH3)CH2CH(OH)CH2C(O)C2H5, -CH2CH(CH3)CH2CH=CHC(O)C2H5, -CH2CH(CH3)CH2CH2CH2C(O)C2H5, -CH2CH(CH3)(CH2)3CH(OH)C2H5, -CH2CH(CH3)CH2CH(OCH3)CH2C(O)C2H5; R3 is selected from C2-C12alkyl optionally substituted with OH, C2-C12alkoxy, C2-C12alkenyl optionally substituted with OH, C1-C8alkylene-R29, wherein in alkylene one or two -CH2- moieties are optionally replaced by -CH(NR30R31)-, -CH(OH)-, -C(=O)-, -NR30R31- or -CH(CH3)- moieties, wherein there are no adjacent -C(=O)- moieties or adjacent -NR30R31- moieties, and wherein R29 is independently at each occurrence selected from hydrogen; aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C1-C4alkyl, OR32, NR33R34; wherein R32, R33, R34 are independently at each occurrence H, halogen, CF3, C1-C3alkyl; and wherein R30 and R31 are independently at each occurrence H, C1-C3alkyl; R4 is wherein R35 is independently selected from hydrogen and C1-C3-alkyl; R36 is independently at each occurrence selected from -cycloalkyl-NR41R42, wherein said cycloalkyl moiety is optionally substituted by C1-C4alkyl, hydroxyl, halogen, OR43; -C3-C6alkylene-NR41R42, wherein said C3-C6alkylene moiety is optionally substituted by hydroxyl, OR43, halogen; cycloalkyl optionally substituted with C1-C4alkyl, halogen, OR43; or wherein R35 and R36 together with the nitrogen atom to which they are attached form independently at each occurrence a heteroaryl, a heterocyclyl or a heterocyclic spiranyl, each independently optionally substituted with C1-C4alkyl, halogen, OR43, NR44R45, wherein R43, R44, R45 are independently at each occurrence H, C1-C4alkyl; and wherein R37, R38, R39 and R40 are independently at each occurrence H or C1-C3alkyl, preferably H or methyl, or independently at each occurrence two of said R37, R38, R39 and R40 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, preferably a carbocyclic ring, and wherein R41 and R42 are independently of each other H or C1-C4alkyl optionally substituted with halogen, hydroxyl or C3-C6cycloalkyl; or together with the nitrogen atoms to which they are attached form independently at each occurrence a heteroaryl or a heterocyclyl, each independently optionally substituted with halogen, C1-C4alkyl, OR43, NR44R45; wherein the arrow indicates the attachment to the C(O)-moiety depicted in formula (I); and pharmaceutically acceptable salts of said compound of formula (I). The present invention further relates to pharmaceutical compositions comprising said compounds and to the use of said compounds in a method of treatment of a protozoan disease, wherein preferably said protozoan disease is selected from malaria, human African trypanosomiasis, Chagas disease or leishmaniasis.

  本发明涉及式(I)的化合物，其中--A--表示一条肽链，所述肽链由5至7个氨基酸组成，其中所述氨基酸选自任何氨基酸，其中所述5至7个氨基酸中至少有两个、优选至少三个为α-氨基异丁酸(Aib)、亮氨酸(Leu)或丙氨酸(Ala)； R1是： 其中，X为N或CH； R5选自H、C1-C16烷基、C1-C16烯基、C(O)-C1-C16烷基、C(O)-C1-C16烯基(其中所述C1-C16烷基、C1-C16烯基、C(O)-C1-C16烷基、C(O)-C1-C16烯基)各自可独立地被卤素、NR11R12、-[O-C2H4]n-OCH3(其中n=2-20)取代；C(O)-R8、C(O)-C1-C3亚烷基-R8、N(H)C(O)-R8、或S(O)2-R9，其中： R8在每次出现时独立地选自芳基、杂芳基、环烷基、杂环基，各自独立地可被C1-C4烷基、卤素、CF3、OR10、NR11R12、C6H5和被卤素、C1-C3烷基、OR10、NR11R12取代的C6H5取代；其中R10、R11、R12在每次出现时独立地为H、C1-C3烷基； R9在每次出现时独立地选自C1-C4烷基、芳基、杂芳基，各自独立地可被C1-C4烷基、卤素、CF3、OR13、NR14R15取代；其中R13、R14、R15在每次出现时独立地为H、C1-C3烷基； R6、R7在每次出现时独立地选自H、C1-C4烷基、C1-C4烯基、C(O)-C1-C3烷基、C(O)-C1-C4烯基(其中所述C1-C4烷基、C1-C4烯基、C(O)-C1-C3烷基、C(O)-C1-C4烯基)各自独立地可被卤素、NR11R12取代；或R6和R7与所连接的X-C基团共同形成独立地在每次出现时为芳基、杂芳基、环烷基、杂环基，各自独立地可被C1-C4烷基、卤素、CF3、OR10、NR11R12、C6H5和被卤素、C1-C3烷基、OR10、NR11R12取代的C6H5取代；其中R10、R11、R12在每次出现时独立地为H、C1-C3烷基；其中箭头指示连接至式(I)中所示的NH基团； R2选自C1-C14烷基、C2-C14烷基可选地被OH、C2-C14烷氧基、C2-C14烯基可选地被OH取代；C1-C8亚烷基-R23，其中亚烷基中的一或两个-CH2-基团可选地被-CH(NR24R25)-、-CH(OH)-、-C(=O)-、-NR24R25-或-CH(CH3)-基团取代，且不存在相邻的-C(=O)-基团或相邻的-NR24R25-基团，且其中： R23在每次出现时独立地选自氢；芳基、杂芳基、环烷基、杂环基，各自独立地可被C1-C4烷基、OR26、NR27R28取代；其中R26、R27、R28在每次出现时独立地为H、卤素、CF3、C1-C3烷基；且其中R24和R25在每次出现时独立地为H、C1-C3烷基； 条件是R2不为-CH2CH(CH3)CH2CH(OH)CH2C(O)C2H5、-CH2CH(CH3)CH2CH=CHC(O)C2H5、-CH2CH(CH3)CH2CH2CH2C(O)C2H5、-CH2CH(CH3)(CH2)3CH(OH)C2H5、-CH2CH(CH3)CH2CH(OCH3)CH2C(O)C2H5； R3选自C2-C12烷基可选地被OH、C2-C12烷氧基、C2-C12烯基可选地被OH取代，或C1-C8亚烷基-R29，其中亚烷基中的一或两个-CH2-基团可选地被-CH(NR30R31)-、-CH(OH)-、-C(=O)-、-NR30R31-或-CH(CH3)-基团取代，且不存在相邻的-C(=O)-基团或相邻的-NR30R31-基团，且其中： R29在每次出现时独立地选自氢；芳基、杂芳基、环烷基、杂环基，各自独立地可被C1-C4烷基、OR32、NR33R34取代；其中R32、R33、R34在每次出现时独立地为H、卤素、CF3、C1-C3烷基；且其中R30和R31在每次出现时独立地为H、C1-C3烷基； R4为： 其中R35独立地选自氢和C1-C3烷基； R36在每次出现时独立地选自-环烷基-NR41R42的环烷基部分可选地被C1-C4烷基、羟基、卤素、OR43取代；-C3-C6亚烷基-NR41R42的C3-C6亚烷基部分可选地被羟基、OR43、卤素取代；环烷基可选地被C1-C4烷基、卤素、OR43取代；或R35和R36与所连接的氮原子共同形成独立地在每次出现时为杂芳基、杂环基或杂环螺旋基，各自独立地可被C1-C4烷基、卤素、OR43、NR44R45取代，其中R43、R44、R45在每次出现时独立地为H、C1-C4烷基；且其中： R37、R38、R39和R40在每次出现时独立地为H或C1-C3烷基，优选H或甲基，或在每次出现时R37、R38、R39和R40中的两个与所连接的碳原子共同形成碳环或杂环环，优选为碳环，且其中： R41和R42彼此独立地为H或C1-C4烷基(可选地被卤素、羟基或C3-C6环烷基取代)；或与所连接的氮原子共同形成独立地在每次出现时为杂芳基或杂环基，各自独立地可被卤素、C1-C4烷基、OR43、NR44R45取代；其中 箭头指示连接至式(I)中所示的C(O)基团；以及式(I)化合物的药学上可接受的盐。 本发明还涉及包含所述化合物的药物组合物，以及所述化合物在治疗原虫病的方法中的用途，其中优选所述原虫病选自疟疾、人类非洲锥虫病、查加斯病或利什曼病。
• Chaetomugilins I–O, new potent cytotoxic metabolites from a marine-fish-derived Chaetomium species. Stereochemistry and biological activities
  作者：Yasuhide Muroga、Takeshi Yamada、Atsushi Numata、Reiko Tanaka

  DOI：10.1016/j.tet.2009.06.125

  日期：2009.9

  Chaetomugilins I-O were isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, as well as chemical transformations. These compounds exhibited significant growth inhibition of cultured P388, HL-60, L1210, and KB cell lines. In addition, chaetomugilin I showed selective cytotoxic activity against 39 human cancer cell lines. (C) 2009 Elsevier Ltd. All rights reserved.