(2Z,4E,6R,7S,9S,10Z,12S,13R,14S,16S,19R,20R,21S,22S,23Z)-7,9,13,19-tetrakis(tert-butyldimethylsilanyloxy)-21-hydroxy-6,12,14,16,20,22-hexamethylhexacosa-2,4,10,23,25-pentaenoic acid | 871236-57-6

• 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: (2Z,4E,6R,7S,9S,10Z,12S,13R,14S,16S,19R,20R,21S,22S,23Z)-7,9,13,19-tetrakis(tert-butyldimethylsilanyloxy)-21-hydroxy-6,12,14,16,20,22-hexamethylhexacosa-2,4,10,23,25-pentaenoic acid
• 英文别名: (2Z,4E,10Z,23Z)-(6R,7S,9S,12S,13R,14S,16S,19R,20R,21S,22S)-7,9,13,19-tetrakis-(tertbutyldimethylsilyloxy)-21-hydroxy-6,12,14,16,20,22-hexamethyl-hexacosa-2,4,10,23,25-pentaenoic acid；(2Z,4E,6R,7S,9S,10Z,12S,13R,14S,16S,19R,20R,21S,22S,23Z)-7,9,13,19-tetrakis(tert-butyldimethylsilyloxy)-21-hydroxy-6,12,14,16,20,22-hexamethylhexacosa-2,4,10,23,25-pentaenoic acid；(2Z,4E,6R,7S,9S,10Z,12S,13R,14S,16S,19R,20R,21S,22S,23Z)-7,9,13,19-tetrakis(tert-Butyldimethylsilyloxy)-21-hydroxy-6,12,14,16,20,22-hexamethylhexacosa-2,4,10,23,25-pentaenoic acid；(2Z,4E,6R,7S,9S,10Z,12S,13R,14S,16S,19R,20R,21S,22S,23Z)-7,9,13,19-tetrakis[[tert-butyl(dimethyl)silyl]oxy]-21-hydroxy-6,12,14,16,20,22-hexamethylhexacosa-2,4,10,23,25-pentaenoic acid
• CAS: 871236-57-6
• 化学式: C₅₆H₁₁₀O₇Si₄
• 分子量: 1007.83
• InChiKey: GBUWBIBKXPETMM-NAIGYUQKSA-N

物化性质

• 沸点：
  822.1±65.0 °C(Predicted)
• 密度：
  0.926±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  16.78
• 重原子数：
  67
• 可旋转键数：
  32
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  94.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2Z,4E,6R,7S,9S,10Z,12S,13R,14S,16S,19R,20R,21S,22S,23Z)-7,9,13,19-tetrakis(tert-butyldimethylsilanyloxy)-21-hydroxy-6,12,14,16,20,22-hexamethylhexacosa-2,4,10,23,25-pentaenoic acid 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 20.5h， 生成 (3Z,5E,11Z)-(7R,8S,10S,13S,14R,15S,17S,20R,21R,22S)-8,10,14,20-tetrakis-(tert-butyldimethylsilyloxy)-7,13,15,17,21-pentamethyl-22-((Z)-(S)-1-methyl-penta-2,4-dienyl)-oxacyclodocosa-3,5,11-trien-2-one
  参考文献：
  名称：

  潜在抗肿瘤药（-）-dictyostatin的全合成。

  摘要：

  [结构：见正文]潜在的抗肿瘤药（-）-dictyostatin已利用布朗的巴豆基硼化法合成，从而获得了11个手性中心中的8个。26个步骤的最长序列的产率约为4％。C9-C10偶联是通过添加立体选择性乙烯基锌酸酯实现的。

  DOI：

  10.1021/ol062737k
• 作为产物：
  描述：

  (2E,4R,5S,7S,8Z,10S,11R,12S,14S,17R,18R,19S,20S,21Z)-19-(4-methoxybenzyloxy)-5,7,11,17-tetrakis(tert-butyldimethylsilanyloxy)-4,10,12,14,18,20-hexamethyltetracosa-2,8,21,23-tetraen-1-ol 在 氢氧化钾 、 18-冠醚-6 、 水 、 双(三甲基硅烷基)氨基钾 、 戴斯-马丁氧化剂 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 9.0h， 生成 (2Z,4E,6R,7S,9S,10Z,12S,13R,14S,16S,19R,20R,21S,22S,23Z)-7,9,13,19-tetrakis(tert-butyldimethylsilanyloxy)-21-hydroxy-6,12,14,16,20,22-hexamethylhexacosa-2,4,10,23,25-pentaenoic acid
  参考文献：
  名称：

  (-)-dictyostatin 和立体异构体的合成和生物学评价。

  摘要：

  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。

  DOI：

  10.1016/j.tet.2007.05.033

文献信息

• Formal Synthesis of Dictyostatin and Synthesis of Two Dictyostatin Analogues
  作者：Julien Gallon、Jorge Esteban、Samir Bouzbouz、Matthew Campbell、Sébastien Reymond、Janine Cossy

  DOI：10.1002/chem.201201001

  日期：2012.9.10

  A formal convergent synthesis of dictyostatin from (R)‐Roche ester is described. Synthetic highlights include a Ni‐catalyzed Nozaki–Hiyama–Kishi coupling between an aldehyde and a Z vinyl iodide to assemble the two main fragments, a diastereoselective Myers alkylation, a stereoselective Evans aldolization, two asymmetric Duthaler crotyltitanations, and a stereoselective Pd‐catalyzed Marshall allenylindium

  描述了一种由（R）-Roche酯正式聚合的dictyostatin合成方法。合成亮点包括醛和Z乙烯基碘之间的镍催化的Nozaki–Hiyama–Kishi偶联以组装两个主要片段，非对映选择性Myers烷基化，立体选择性Evans醛醇缩合，两个不对称Duthaler crotyltitanations和立体选择性Pd催化马歇尔（Marshall）除烯丙基铟外，还可以安装双泛抑素的立体异构中心。的合成（9 - [R ）-外延-dictyostatin和一个新的环收缩dictyostatin也实现异构体。
• 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。
• [EN] ANALOGS OF DICTYOSTATIN, INTERMEDIATES THEREFOR AND METHODS OF SYNTHESIS THEREOF<br/>[FR] ANALOGUES DE LA DICTYOSTATINE, INTERMEDIAIRES ET METHODES DE SYNTHESE
  申请人：UNIV PITTSBURGH

  公开号：WO2005117588A3

  公开（公告）日：2007-03-15
• Total Synthesis of (−)-Dictyostatin: Confirmation of Relative and Absolute Configurations
  作者：Youseung Shin、Jean-Hugues Fournier、Yoshikazu Fukui、Arndt M. Brückner、Dennis P. Curran

  DOI：10.1002/anie.200460593

  日期：2004.9.6