(2Z,4E,6R,7S,9S,10Z,12S,13R,14S,19R,20R,21S,22S,23Z)-methyl 7,9,13,19-tetrakis(tert-butyldimethylsilyloxy)-21-hydroxy-6,12,14,20,22-pentamethylhexacosa-2,4,10,23,25-pentaenoate | 861822-04-0

• 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,19R,20R,21S,22S,23Z)-methyl 7,9,13,19-tetrakis(tert-butyldimethylsilyloxy)-21-hydroxy-6,12,14,20,22-pentamethylhexacosa-2,4,10,23,25-pentaenoate
• 英文别名: (2Z,4E,6R,7S,9S,102,12S,13R,14S,19R,20R,21S,22S,23Z)-methyl-7,9,13,19-tetrakis(tert-butyldimethylsilyloxy)-21-hydroxy-6,12,14,20,22-pentamethylhexacosa-2,4,10,23,25-pentaenoate；(2z,4e,6r,7s,9s,10z,12s,13r,14s,19r,20r,21s,22s,23z)-Methyl-7,9,13,19-tetrakis(tert-butyldimethylsilyloxy)-21-hydroxy-6,12,14,20,22-pentamethylhexacosa-2,4,10,23,25-pentaenoate；methyl (2Z,4E,6R,7S,9S,10Z,12S,13R,14S,19R,20R,21S,22S,23Z)-7,9,13,19-tetrakis[[tert-butyl(dimethyl)silyl]oxy]-21-hydroxy-6,12,14,20,22-pentamethylhexacosa-2,4,10,23,25-pentaenoate
• CAS: 861822-04-0
• 化学式: C₅₆H₁₁₀O₇Si₄
• 分子量: 1007.83
• InChiKey: ROIQLNVYZHTTHE-ZZCGBRROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  16.62
• 重原子数：
  67
• 可旋转键数：
  33
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 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,19R,20R,21S,22S,23Z)-methyl 7,9,13,19-tetrakis(tert-butyldimethylsilyloxy)-21-hydroxy-6,12,14,20,22-pentamethylhexacosa-2,4,10,23,25-pentaenoate 在 氢氧化钾 、 2,4,6-三氯苯甲酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 8(S),10(S),14(R),20(R)-tetrakis(tert-butyldimethylsilyloxy)-7(R),13(S),15(S),21(S)-tetramethyl-22(S)-(1(S)-methyl-penta-2,4-dienyl)-oxa-cyclodocosa-3,5,11-trien-2-one
  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：

  (2Z,4E,6R,7S,9S,10Z,12S,13R,14S,19R,20R,21S,22S,23Z)-methyl 21-(4-methoxybenzyloxy)-7,9,13,19-tetrakis(tert-butyldimethylsilyloxy)-6,12,14,20,22-pentamethylhexacosa-2,4,10,23,25-pentaenoate 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 以82%的产率得到(2Z,4E,6R,7S,9S,10Z,12S,13R,14S,19R,20R,21S,22S,23Z)-methyl 7,9,13,19-tetrakis(tert-butyldimethylsilyloxy)-21-hydroxy-6,12,14,20,22-pentamethylhexacosa-2,4,10,23,25-pentaenoate
  参考文献：
  名称：

  （-）-dictyostatin的C16类似物的全合成和生物学评估。

  摘要：

  （-）-dictyostatin关键C16区的结构活性关系是通过类似物的全合成，然后进行详细的生物学表征来建立的。一种通用的合成策略用于制备毫克量的16-正甲基顺式他汀，16-表-顺式他汀和C16-正甲基-C15Z异构体。在此过程中，还制备了许多其他的E / Z异构体和差向异构体，并发现了一种新型的内酯环收缩，可制得具有20元大内酯（而不是22元大内酯）的异-dictyostatins。16-去甲基-15,16-脱氢dictyostatin的合成是通过最大汇聚途径合成的dictyostatin中的第一个，其中三个主要片段组装在一起，背靠背连接，然后通过重新官能化和大环内酯化处理。基于细胞的和生化评估显示，新药中最有效的是16-normethyl-15,16-dehydrodictyostatin和16-normethyldictyostatin，它们的活性仅比（-）-dictyostati

  DOI：

  10.1021/jm061385k

文献信息

• 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。
• Total Synthesis and Biological Evaluation of C16 Analogs of (−)-Dictyostatin
  作者：Won-Hyuk Jung、Cristian Harrison、Youseung Shin、Jean-Hugues Fournier、Raghavan Balachandran、Brianne S. Raccor、Rachel P. Sikorski、Andreas Vogt、Dennis P. Curran、Billy W. Day

  DOI：10.1021/jm061385k

  日期：2007.6.1

  The structure-activity relationship of the crucial C16 region of (-)-dictyostatin was established through total synthesis of analogs followed by detailed biological characterization. A versatile synthetic strategy was used to prepare milligram quantities of 16-normethyldictyostatin, 16-epi-dictyostatin, and the C16-normethyl-C15Z isomer. Along the way, a number of other E/Z isomers and epimers were

  （-）-dictyostatin关键C16区的结构活性关系是通过类似物的全合成，然后进行详细的生物学表征来建立的。一种通用的合成策略用于制备毫克量的16-正甲基顺式他汀，16-表-顺式他汀和C16-正甲基-C15Z异构体。在此过程中，还制备了许多其他的E / Z异构体和差向异构体，并发现了一种新型的内酯环收缩，可制得具有20元大内酯（而不是22元大内酯）的异-dictyostatins。16-去甲基-15,16-脱氢dictyostatin的合成是通过最大汇聚途径合成的dictyostatin中的第一个，其中三个主要片段组装在一起，背靠背连接，然后通过重新官能化和大环内酯化处理。基于细胞的和生化评估显示，新药中最有效的是16-normethyl-15,16-dehydrodictyostatin和16-normethyldictyostatin，它们的活性仅比（-）-dictyostati
• 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。