(3S,4R,5S)-4-Amino-5-methyl-3-triisopropylsilanyloxy-heptanoic acid (1S,2S,3R)-4-(tert-butyl-dimethyl-silanyloxy)-1-isopropyl-2-methoxymethoxy-3-methyl-butyl ester | 126587-57-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,4R,5S)-4-Amino-5-methyl-3-triisopropylsilanyloxy-heptanoic acid (1S,2S,3R)-4-(tert-butyl-dimethyl-silanyloxy)-1-isopropyl-2-methoxymethoxy-3-methyl-butyl ester
• 英文别名: [(3S,4S,5R)-6-[tert-butyl(dimethyl)silyl]oxy-4-(methoxymethoxy)-2,5-dimethylhexan-3-yl] (3S,4R,5S)-4-amino-5-methyl-3-tri(propan-2-yl)silyloxyheptanoate
• CAS: 126587-57-3
• 化学式: C₃₃H₇₁NO₆Si₂
• 分子量: 634.101
• InChiKey: MXGUJXRJGSPYQM-IQYCLPFMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.53
• 重原子数：
  42
• 可旋转键数：
  22
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  89.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S,4R,5S)-4-Amino-5-methyl-3-triisopropylsilanyloxy-heptanoic acid (1S,2S,3R)-4-(tert-butyl-dimethyl-silanyloxy)-1-isopropyl-2-methoxymethoxy-3-methyl-butyl ester 在 4-二甲氨基吡啶 、 sodium chlorite 、 sodium dihydrogenphosphate 、 戴斯-马丁氧化剂 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 生成 [(2R,3S)-4-[[(3S,4R,5S)-1-[(3S,4S,5S)-4-(methoxymethoxy)-2,5-dimethyl-6-oxo-6-(2,3,4,5,6-pentafluorophenoxy)hexan-3-yl]oxy-5-methyl-1-oxo-3-tri(propan-2-yl)silyloxyheptan-4-yl]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutan-2-yl] (3S)-2-[(2S)-1-[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]pyrrolidine-2-carbonyl]-3,4-dihydro-1H-isoquinoline-3-carboxylate
  参考文献：
  名称：

  [Tic5]双氢精蛋白B的合成及生物活性。

  摘要：

  已经合成了含有Tic（1,2,3,4-四氢异喹啉-3-羧酸）作为酪氨酸的构象受约束替代物的双联蛋白B类似物，并显示出与蛋白质生物合成抑制剂相当的功效。合成亮点包括在敏感的Tic杂环存在下将醇氧化为酸，以及改良的Schmidt型单锅大环化反应。

  DOI：

  10.1016/s0960-894x(98)00662-3
• 作为产物：
  描述：

  L-缬氨酸 在 palladium on activated charcoal 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 钾硼氢 、 三氟甲磺酸 、 硫酸 、 氨 、 氢气 、 sodium 、 三氧化硫吡啶 、 四氯化锡 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 环己烷 、 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， -78.0~25.0 ℃ 、5.33 kPa 条件下， 反应 122.0h， 生成 (3S,4R,5S)-4-Amino-5-methyl-3-triisopropylsilanyloxy-heptanoic acid (1S,2S,3R)-4-(tert-butyl-dimethyl-silanyloxy)-1-isopropyl-2-methoxymethoxy-3-methyl-butyl ester
  参考文献：
  名称：

  didemnins A、B 和 C 的全合成和结构研究

  摘要：

  Didemnins A、B 和 C 以立体控制的方式有效制备，产生常见的大环，并在单独的步骤中，在 L-苏氨酸的氨基上引入取代基作为光学纯单元。我们设想 L-亮氨酸和 HIP 基团 (2S,4S) 之间以及 L-苏氨酸和异司他汀 (3S,4R,5S) 之间的断开将提供两个单元：HIP-异司他汀单元 (I) 和四肽单元 (II) )

  DOI：

  10.1021/ja00177a030

文献信息

• Total Syntheses of Conformationally Constrained Didemnin B Analogues. Replacements of <i>N</i>,<i>O</i>-Dimethyltyrosine with <scp>l</scp>-1,2,3,4-Tetrahydroisoquinoline and <scp>l</scp>-1,2,3,4-Tetrahydro-7-methoxyisoquinoline
  作者：James E. Tarver、Amy J. Pfizenmayer、Madeleine M. Joullié

  DOI：10.1021/jo0105991

  日期：2001.11.1

  The design and synthesis of two conformationally constrained analogues of didemnin B are described. The [N,O-Me(2)Tyr(5)]residue of didemnin B was replaced with L-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) and L-1,2,3,4-tetrahydro-7-methoxyisoquinoline-3-carboxylic acid (MeO-Tic), which mimic the N,O-dimethylated tyrosine while constraining the conformation of the molecule. Preliminary

  描述和设计了两种构型受约束的二氢蝶呤B的类似物。豆双宁B的[N，O-Me（2）Tyr（5）]残基被L-1,2,3,4-四氢异喹啉-3-羧酸（Tic）和L-1,2,3取代， 4-四氢-7-甲氧基异喹啉-3-羧酸（MeO-Tic），可模仿N，O-二甲基化的酪氨酸，同时限制分子的构象。初步结果表明[N，O-Me（2）Tyr（5）]残基的构象与Tic替代所施加的构象非常匹配。
• Synthesis and biological activities of [N-MeLeu5]- and [N-MePhe5]-didemnin B
  作者：Amy J. Pfizenmayer、Joshi M. Ramanjulu、Matthew D. Vera、Xiaobin Ding、Dong Xiao、Chen Wei-Chuan、Madeleine M. Joullié

  DOI：10.1016/s0040-4020(98)01042-4

  日期：1999.1

  X-ray, NMR, and SAR data, the N,O-diMeTyr5 unit of didemnin B was believed to be important for biological activity. To determine the importance of aromaticity and the role of the methoxy group in this unit, two analogs were synthesized in which the N,O-diMeTyr5 moiety was replaced with N-MeLeu and N-MePhe. Preliminary testing showed that the analogs retained antitumor activity and the ability to inhibit

  基于来自X射线，NMR和SAR数据的信息，认为二氢蝶呤B的N，O -diMeTyr 5单元对于生物活性很重要。为了确定芳香性的重要性和甲氧基在该单元中的作用，合成了两个类似物，其中N，O- diMeTyr 5部分被N- MeLeu和N- MePhe取代。初步测试表明，该类似物在体外具有抗肿瘤活性和抑制蛋白质生物合成的能力。
• Synthetic studies of didemnins. IV. Synthesis of the macrocycle
  作者：William R. Ewing、Bruce D. Harris、Wen-Ren Li、Madeleine M. Joullie

  DOI：10.1016/s0040-4039(01)80647-x

  日期：1989.1

  A stereocontrolled route to the 23-membered macrocycle found in the didemnins is described.

  描述了在双氢精蛋白中发现的到23元大环的立体控制途径。
• Synthesis of New Didemnin B Analogs for Investigations of Structure/Biological Activity Relationships
  作者：Scott C. Mayer、Joshi Ramanjulu、Matthew D. Vera、Amy J. Pfizenmayer、Madeleine M. Joullie

  DOI：10.1021/jo00097a022

  日期：1994.9

  Modifications were introduced in the side chain of didemnin B to afford several analogs (1f-1j) for biological testing in order to identify the features responsible for the bioactivity of the natural products (1a-1c). To achieve our goal, two changes were made in the proline ring of the beta-turn side chain. Initially, a hydroxyl group was incorporated at the C-4 position of the ring to increase the polar nature of the molecule. Secondly, unsaturation was introduced at C-3 and C-4 to increase the rigidity of the ring and to provide a site for tritiation to follow the drug pathway in biological systems. Improvements were also introduced in the macrocycle construction to produce gram quantities of this unit (1d) for the preparation of the planned analogs. The linear precursor to the macrocycle was oxidized more effectively with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane reagent), and cyclization yields were increased substantially by using a new coupling reagent, pentafluorophenyl diphenylphosphinate (FDPP). (1H-1,2,3-benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and pentafluorophenyl trifluoroacetate were also used to improve other coupling reactions.
• [Lys3]didemnins as potential affinity ligands
  作者：Matthew D Vera、Amy J Pfizenmayer、Xiaobin Ding、Dong Xiao、Madeleine M Joullié

  DOI：10.1016/s0960-894x(00)00585-0

  日期：2001.1

  The synthesis and biological activity of N-epsilon-Z-[Lys(3)]didemnin B are reported. This novel analogue retains antiproliferative, cytotoxic, and protein biosynthesis inhibition activities, but at reduced levels. This result suggests the use of [Lys(3)]didemnin derivatives as potential affinity probes for studying the molecular target(s) of the didemnin class of natural products. (C) 2000 Elsevier Science Ltd. All rights reserved.