(4S)-4-N-tert-butoxycarbonylamino-2,5-dimethyl-2-trans-hexenoic acid, ethyl ester | 244033-73-6

• 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: (4S)-4-N-tert-butoxycarbonylamino-2,5-dimethyl-2-trans-hexenoic acid, ethyl ester
• 英文别名: ethyl [L-(trans)]-4-[(t-butoxycarbonyl)amino]-2,5-dimethyl-2-hexenoate；ethyl (2E,4S)-4-(tert-butoxycarbonylamino)-2,5-dimethylhex-2-enoate；ethyl (E,4S)-2,5-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]hex-2-enoate
• CAS: 244033-73-6
• 化学式: C₁₅H₂₇NO₄
• 分子量: 285.384
• InChiKey: FZPOZCWKALNUKR-LMMOQWNQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S)-4-N-tert-butoxycarbonylamino-2,5-dimethyl-2-trans-hexenoic acid, ethyl ester 在 三乙酰氧基硼氢化钠 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 (4S)-4-(N-benzyl-N-hexa-2',4'-dienyl)amino-2,5-dimethyl-2-trans-hexanoic acid, ethyl ester
  参考文献：
  名称：

  Diels−Alder Reactions of Amino Acid-Derived Trienes

  摘要：

  Triene precursors (1a-e, 2a-k) were constructed for substrate-controlled asymmetric Diels-Alder reactions. Boc-L-phenylalanal and Boc-L-valinal were condensed with triethyl phosphonoacetate or 2-phosphonopropionate to generate the alpha,beta-unsaturated esters as dienophiles. Removal of the Boc group to give free amines 4a-d, which after, or without N-benzylation, were treated with 3,5-hexadienoyl chloride to give 1a-e, or with 2,4-hexadienoyl chloride to afford 2a-f. The trienes 2g-i were prepared via reductive alkylation of amines 4a-i with 2,4-hexadienal. The secondary amide triene la failed to yield any Diels-Alder product when heated at 170 degrees C. The tertiary amide trienes 1b-e produced in refluxing toluene the major cycloaddition products that were cia-fused and derived from the exo transition states. Trienes 2a-k underwent surprisingly facile Diels-Alder reactions to produce the major trans-fused isomers that Were derived from the endo transition states. For trienes 2b-h and 2j,k, Diels-Alder reactions proceeded at room temperature. For the primary amide 2a, the Diels-Alder reaction proceeded smoothly in refluxing toluene. The tertiary amide triene 22 was constructed to have two electron-withdrawing ester substituents at the termini of the triene. The Diels-Alder reaction of 22 took place spontaneously at room temperature upon benzoylation of the secondary amine 21 and produced a single isomer derived from the endo transition state. 1,3-Allylic strain is discussed as an important factor in control of the diastereoselectivity.

  DOI：

  10.1021/jo990459f
• 作为产物：
  描述：

  N-(叔丁氧基羰基)-L-缬氨酸N-甲氧基-N-甲基酰胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.5h， 生成 (4S)-4-N-tert-butoxycarbonylamino-2,5-dimethyl-2-trans-hexenoic acid, ethyl ester
  参考文献：
  名称：

  具有α，β-不饱和羰基部分的新型简化半胱氨酸衍生物的合成

  摘要：

  在这封信中，我们报告了一种方便而有效的方法，用于合成半精胺素的新的简化衍生物，其中α，α-二甲基苄基部分A被α，β-不饱和芳基取代为Michael受体。这些衍生物大多数对三种人类肿瘤细胞系（KB，Hep-G 2和MCF 7）具有很强的细胞毒活性。类似物17b和17f显示出与紫杉醇和玫瑰树碱相当的对KB和Hep-G 2癌细胞系的高细胞毒性。

  DOI：

  10.1016/j.bmcl.2014.03.091

文献信息

• Stereoselective synthesis of vinylogous peptides
  作者：Claude Grison、Stéphane Genève、Etienne Halbin、Philippe Coutrot

  DOI：10.1016/s0040-4020(01)00433-1

  日期：2001.6

  A trans or cis ethenyl group has been inserted between the α-carbon and the carboxyl group of α-aminoacids by Horner stereoselective olefination of α-aminoaldehydes. Numerous pure cis and trans vinylogous α-aminoacids have been obtained thus and coupled with aminopartners by classical methods. The versatility of the method was illustrated by the preparation of a [trans vinylogous-Gly3]Leu-enkephalin

  通过α-氨基醛的霍纳立体选择性烯化，将反式或顺式乙烯基插入α-氨基酸的α-碳和羧基之间。因此已经获得了许多纯的顺式和反式乙烯基α-氨基酸，并通过经典方法与氨基配偶体偶联。该方法的多功能性通过制备[反式乙烯基-Gly 3 ]亮脑啡肽来说明。
• Synthesis and Antimitotic/Cytotoxic Activity of Hemiasterlin Analogues
  作者：James A. Nieman、John E. Coleman、Debra J. Wallace、Edward Piers、Lynette Y. Lim、Michel Roberge、Raymond J. Andersen

  DOI：10.1021/np020375t

  日期：2003.2.1

  The antimitotic sponge tripeptide hemiasterlin (1) and a number of structural analogues have been synthesized and evaluated in cell-based assays for both cytotoxic and antimitotic activity in order to explore the SAR for this promising anticancer drug lead. One synthetic analogue, SPA110 (8), showed more potent in vitro cytotoxicty and antimitotic activity than the natural product hemiasterlin (1), and consequently it has been subjected to thorough preclinical evaluation and targeted for clinical evaluation. The details of the synthesis of hemiasterlin (1) and the analogues and a discussion of how their biological activities vary with their structures are presented in this paper.
• Guindon Y., Slassi A., Rancourt J., Bantle G., Bencheqroun M., Murtagh L.+, J. Org. Chem, 60 (1995) N 2, S 288-289
  作者：Guindon Y., Slassi A., Rancourt J., Bantle G., Bencheqroun M., Murtagh L.+

  DOI：——

  日期：——
• Synthesis of new simplified hemiasterlin derivatives with α,β-unsaturated carbonyl moiety
  作者：Chinh Pham The、Tuyet Anh Dang Thi、Thi Phuong Hoang、Quoc Anh Ngo、Duy Tien Doan、Thu Ha Nguyen Thi、Tham Pham Thi、Thu Ha Vu Thi、M. Jean、P. van de Weghe、Tuyen Nguyen Van

  DOI：10.1016/j.bmcl.2014.03.091

  日期：2014.5

  In this Letter, we report a convenient and efficient method for the synthesis of new simplified derivatives of hemiasterlin in which the α,α-dimethylbenzylic moiety A is replaced by α,β-unsaturated aryl groups as Michael acceptor. Most of these derivatives have a strong cytotoxic activity on three human tumor cell lines (KB, Hep-G2 and MCF7). Analogs 17b and 17f showed a high cytotoxicity against KB

  在这封信中，我们报告了一种方便而有效的方法，用于合成半精胺素的新的简化衍生物，其中α，α-二甲基苄基部分A被α，β-不饱和芳基取代为Michael受体。这些衍生物大多数对三种人类肿瘤细胞系（KB，Hep-G 2和MCF 7）具有很强的细胞毒活性。类似物17b和17f显示出与紫杉醇和玫瑰树碱相当的对KB和Hep-G 2癌细胞系的高细胞毒性。
• Diels−Alder Reactions of Amino Acid-Derived Trienes
  作者：William V. Murray、Sengen Sun、Ignatius J. Turchi、Frank K. Brown、A. Diane Gauthier

  DOI：10.1021/jo990459f

  日期：1999.8.1

  Triene precursors (1a-e, 2a-k) were constructed for substrate-controlled asymmetric Diels-Alder reactions. Boc-L-phenylalanal and Boc-L-valinal were condensed with triethyl phosphonoacetate or 2-phosphonopropionate to generate the alpha,beta-unsaturated esters as dienophiles. Removal of the Boc group to give free amines 4a-d, which after, or without N-benzylation, were treated with 3,5-hexadienoyl chloride to give 1a-e, or with 2,4-hexadienoyl chloride to afford 2a-f. The trienes 2g-i were prepared via reductive alkylation of amines 4a-i with 2,4-hexadienal. The secondary amide triene la failed to yield any Diels-Alder product when heated at 170 degrees C. The tertiary amide trienes 1b-e produced in refluxing toluene the major cycloaddition products that were cia-fused and derived from the exo transition states. Trienes 2a-k underwent surprisingly facile Diels-Alder reactions to produce the major trans-fused isomers that Were derived from the endo transition states. For trienes 2b-h and 2j,k, Diels-Alder reactions proceeded at room temperature. For the primary amide 2a, the Diels-Alder reaction proceeded smoothly in refluxing toluene. The tertiary amide triene 22 was constructed to have two electron-withdrawing ester substituents at the termini of the triene. The Diels-Alder reaction of 22 took place spontaneously at room temperature upon benzoylation of the secondary amine 21 and produced a single isomer derived from the endo transition state. 1,3-Allylic strain is discussed as an important factor in control of the diastereoselectivity.