(-)-(2S,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-5-((4-methoxybenzyl)oxy)-2,4-dimethylpentan-1-ol | 792911-22-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (-)-(2S,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-5-((4-methoxybenzyl)oxy)-2,4-dimethylpentan-1-ol
• 英文别名: (2S,3R,4S)-3-(tert-butyldimethylsilyloxy)-5-(4'-methoxybenzyloxy)-2,4-dimethylpentan-1-ol；(2S,3R,4S)-5-(4-methoxybenzyloxy)-3-(tert-butyldimethylsilyloxy)-2,4-dimethylpentan-1-ol；(2S,3R,4S)-3-[tert-butyl(dimethyl)silyl]oxy-5-[(4-methoxyphenyl)methoxy]-2,4-dimethylpentan-1-ol
• CAS: 792911-22-9
• 化学式: C₂₁H₃₈O₄Si
• 分子量: 382.616
• InChiKey: GSAMOXBBVYEPFS-ABSDTBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.87
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-(2S,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-5-((4-methoxybenzyl)oxy)-2,4-dimethylpentan-1-ol 在 三氧化硫吡啶 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 生成 (2R,3S,4S)-3-((tert-butyldimethylsilyl)oxy)-5-((4-methoxybenzyl)oxy)-2,4-dimethylpentanal
  参考文献：
  名称：

  Synthesis and Biological Evaluation of (−)-16-Normethyldictyostatin:  A Potent Analogue of (−)-Dictyostatin

  摘要：

  (-)-16-去甲基火绒草平素已通过全合成制得，它是一种强有力的抗肿瘤剂，作用于表达野生型微管蛋白的细胞以及一种对紫杉醇耐药的突变细胞系，但在另一种紫杉醇耐药细胞系中，其活性远低于火绒草平素，这种情况下Val取代了Phe270的位置。这提供了有力的证据，表明火绒草平素中的C16甲基基团在β-微管蛋白的紫杉醇结合位点上朝向Phe270。

  DOI：

  10.1021/ol050808u
• 作为产物：
  描述：

  (2R)-3-[(4-methoxybenzyl)oxy]-2-methylpropanol 在 2,6-二甲基吡啶 、 锂硼氢 、 草酰氯 、 三氟甲磺酸二丁硼 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 6.62h， 生成 (-)-(2S,3R,4S)-3-((tert-butyldimethylsilyl)oxy)-5-((4-methoxybenzyl)oxy)-2,4-dimethylpentan-1-ol
  参考文献：
  名称：

  Nhatrangin A：拟议结构及其六种非对映异构体的总合成

  摘要：

  描述了拟南芥A结构的全合成。该策略依赖于两个醇醛反应，将手性中心安装在C3 / C4和C3'/ C4'处，高级中间炔烃和Weinreb酰胺之间通过锂介导的偶联完成C1-C13烷基支架，以及山口酯化设置侧链。合成nhatrangin和天然nhatrangin之间的光谱数据差异导致我们合成了nhatrangin A拟议结构的另外六个非对映异构体。

  DOI：

  10.1021/acs.joc.6b03060

文献信息

• Synthesis and biological evaluation of (−)-dictyostatin and stereoisomers
  作者：Youseung Shin、Jean-Hugues Fournier、Arndt Brückner、Charitha Madiraju、Raghavan Balachandran、Brianne S. Raccor、Michael C. Edler、Ernest Hamel、Rachel P. Sikorski、Andreas Vogt、Billy W. Day、Dennis P. Curran

  DOI：10.1016/j.tet.2007.05.033

  日期：2007.8

  Total syntheses of (-)-dictyostatin, 6,16-bis-epi-dictyostatin, 6,14,19-tris-epi-dictyostatin and a number of other isomers and analogs are reported. Three main fragments-top, middle and bottom-were first assembled and then joined by olefination or anionic addition reactions. After appending the two dienes at either end of the molecule, macrolactonization and deprotection completed the syntheses. The

  报告了 (-)-dictyostatin、6,16-bis-epi-dictyostatin、6,14,19-tris-epi-dictyostatin 和许多其他异构体和类似物的总合成。三个主要片段——顶部、中间和底部——首先组装，然后通过烯化或阴离子加成反应连接。在分子的任一端附加两个二烯后，大环内酯化和脱保护完成合成。这项工作证明了 (-)-dictyostatin 的相对和绝对构型。这些化合物通过基于细胞的微管质量增加和抗增殖活性的测量、体外微管蛋白聚合试验以及与紫杉醇在微管上的结合位点的竞争试验进行评估。
• Synthesis and Biological Evaluation of (−)-16-Normethyldictyostatin:  A Potent Analogue of (−)-Dictyostatin
  作者：Youseung Shin、Jean-Hugues Fournier、Raghavan Balachandran、Charitha Madiraju、Brianne S. Raccor、Guangyu Zhu、Michael C. Edler、Ernest Hamel、Billy W. Day、Dennis P. Curran

  DOI：10.1021/ol050808u

  日期：2005.7.1

  (-)-16-Normethyldictyostatin has been made by total synthesis and is a potent antitumor agent in cells expressing wild-type tubulin and in one mutant cell line that is resistant to paclitaxel, but it is much less active than dictyostatin in another paclitaxel-resistant cell line where Val is substituted for Phe270. This provides strong evidence that the C16 methyl group of the dictyostatins is oriented toward Phe270 in the paclitaxel-binding site on beta-tubulin.

  (-)-16-去甲基火绒草平素已通过全合成制得，它是一种强有力的抗肿瘤剂，作用于表达野生型微管蛋白的细胞以及一种对紫杉醇耐药的突变细胞系，但在另一种紫杉醇耐药细胞系中，其活性远低于火绒草平素，这种情况下Val取代了Phe270的位置。这提供了有力的证据，表明火绒草平素中的C16甲基基团在β-微管蛋白的紫杉醇结合位点上朝向Phe270。
• Investigations of the stereoselectivity of the intramolecular Diels–Alder reaction of a spiculoic acid model system
  作者：Julia S. Crossman、Michael V. Perkins

  DOI：10.1016/j.tet.2008.02.109

  日期：2008.5

  thermally induced IMDA reactions. The configuration of C5 in the stereotriad was found to dominate any inherent endo/exo selectivity of the IMDA reaction. The isomer (2E,5S)-20 underwent the IMDA to give the spiculoic acid stereochemistry in 84% yield and 94% ds. The required stereotriads were synthesised using stereoselective substrate-controlled aldol reactions; an anti-boron aldol reaction, controlled by

  制备了七水杨酸的线性模型前体，并进行了热诱导的IMDA反应。发现立体三联体中C5的构型支配了IMDA反应的任何固有的内/外选择性。对异构体（2 E，5 S）-20进行IMDA，以84％的收率和94％ds的收率得到杜仲酸的立体化学。使用立体选择性底物控制的醛醇缩合反应合成所需的立体三单元组；由（S）-2-苯甲酰氧基戊烷-3-one（（S）-27）的π偏向控制的抗硼羟醛反应导致（5 R）-（22）和在手性N-酰基噻唑烷硫酮（42）的立体控制下合成钛的羟醛反应导致（5S）-（22）。使用标准的Wittig，HWE和“改性” Julia烯烃链进行的扩链安装了二烯和亲二烯体组分，从而为IMDA反应提供了线性前体。
• Analogs of dictyostatin, intermediates therefor and methods of synthesis thereof
  申请人：Curran P. Dennis

  公开号：US20060025395A1

  公开（公告）日：2006-02-02

  Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein R 1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R 2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e ; R a , R b and R c are independently an alkyl group or an aryl group; R d is an alkyl group, an aryl group, an alkoxylalkyl group, —R i SiR a R b R c or a benzyl group, wherein R i is an alkylene group; R e is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NR g R h , wherein R g and R h are independently H, an alkyl group or an aryl group; R 3 is (CH 2 ) n where n is and integer in the range of 0 to 5, —CH 2 CH(CH 3 )—, —CH═CH—, —CH═C(CH 3 )—, or —C≡C—; R 4 is wherein R 23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e ; R 23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e , or R 23a and R 23b together form a portion of six-membered acetal ring incorporating CR t R u ; R t and R u are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R 5 is H or OR 2b , wherein R 2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e ; provided that the compound is not dictyostatin 1.

  Dictyostatin及其类似物作为新的抗癌剂表现出极大的潜力。本发明提供了Dictyostatin类似物，用于合成Dictyostatin类似物的合成中间体以及合成此类类似物和中间体的合成方法。Dictyostatin类似物可以具有以下结构或其对映体，其中R1为H、烷基、芳基、烯基、炔基或卤素原子；R2为H、保护基、烷基、苄基、三苄基甲基基、-SiRaRbRc、CH2ORd或CORe；Ra、Rb和Rc独立地为烷基或芳基；Rd为烷基、芳基、烷氧基烷基、-RiSiRaRbRc或苄基，其中Ri为烷基；Re为烷基、烯丙基、苄基、芳基、烷氧基或-NRgRh，其中Rg和Rh独立地为H、烷基或芳基；R3为(CH2)n，其中n在0到5的整数范围内，-CH2CH(CH3)-、-CH═CH-、-CH═C(CH3)-或-C≡C-；R4为其中R23a为H、保护基、烷基、苄基、三苄基甲基基、-SiRaRbRc、CH2ORd或CORe；R23b为H、保护基、烷基、苄基、三苄基甲基基、-SiRaRbRc、CH2ORd或CORe，或R23a和R23b一起形成包含CRtRu的六元缩醛环的一部分；Rt和Ru独立地为H、烷基、芳基或烷氧基芳基；R5为H或OR2b，其中R2b为H、保护基、烷基、芳基、苄基、三苄基甲基基、-SiRaRbRc、CH2ORd或CORe；但化合物不是Dictyostatin 1。
• Analogs of dictyostatin, intermediates therefor and methods of systhesis thereof
  申请人：Curran Dennis P.

  公开号：US20080188651A1

  公开（公告）日：2008-08-07

  Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein R 1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R 2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e ; R a , R b and R c are independently an alkyl group or an aryl group; R d is an alkyl group, an aryl group, an alkoxylalkyl group, —R i SiR a R b R c or a benzyl group, wherein R i is an alkylene group; R e is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NR g R h , wherein R g and R h are independently H, an alkyl group or an aryl group; R 3 is (CH 2 ) n where n is and integer in the range of 0 to 5, —CH 2 CH(CH 3 ), —CH═CH—, —CH═C(CH 3 ), or —C≡C—; R 4 is wherein R 23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e , R 23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e , or R 23a and R 23b together form a portion of six-membered acetal ring incorporating CR t R u ; R t and R u are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R 5 is H or OR 2b , wherein R 2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e ; provided that the compound is not dictyostatin 1.

  Dictyostatin及其类似物作为新的抗癌剂表现出极大的潜力。本发明提供Dictyostatin类似物，用于合成Dictyostatin类似物的合成中间体，以及用于合成此类类似物和中间体的合成方法。Dictyostatin类似物可以具有以下结构或其对映异构体，其中R1为H、烷基、芳基、烯基、炔基或卤素原子；R2为H、保护基、烷基、苯甲基、三苯基甲基、-SiRaRbRc、CH2ORd或CORe；Ra、Rb和Rc独立地为烷基或芳基；Rd为烷基、芳基、烷氧基烷基、-RiSiRaRbRc或苯甲基，其中Ri为烷基；Re为烷基、烯丙基、苯甲基、芳基、烷氧基或-NRgRh，其中Rg和Rh独立地为H、烷基或芳基；R3为（CH2）n，其中n为0至5之间的整数，-CH2CH（CH3）、-CH═CH-、-CH═C（CH3）或-C≡C-；R4为其中R23a为H、保护基、烷基、苯甲基、三苯基甲基、-SiRaRbRc、CH2ORd或CORe，R23b为H、保护基、烷基、苯甲基、三苯基甲基、-SiRaRbRc、CH2ORd或CORe，或R23a和R23b一起形成包含CRtRu的六元缩醛环的一部分；Rt和Ru独立地为H、烷基、芳基或烷氧基芳基；R5为H或OR2b，其中R2b为H、保护基、烷基、芳基、苯甲基、三苯基甲基、-SiRaRbRc、CH2ORd或CORe；前提是该化合物不是Dictyostatin 1。