(Z)-(5S,6S,7S,8R)-11-iodo-8-(4-methoxybenzyloxy)-5,7-dimethylundeca-1,3-dien-6-yl tert-butyldimethylsilyl ether | 623926-35-2

• 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: (Z)-(5S,6S,7S,8R)-11-iodo-8-(4-methoxybenzyloxy)-5,7-dimethylundeca-1,3-dien-6-yl tert-butyldimethylsilyl ether
• CAS: 623926-35-2
• 化学式: C₂₇H₄₅IO₃Si
• 分子量: 572.643
• InChiKey: FESWBNMARQYKST-AANIIQDUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  32.0
• 可旋转键数：
  14.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  27.69
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (Z)-(5S,6S,7S,8R)-11-iodo-8-(4-methoxybenzyloxy)-5,7-dimethylundeca-1,3-dien-6-yl tert-butyldimethylsilyl ether 在 四丁基氟化铵 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 64.75h， 生成 (Z,Z,Z)-(5S,6S,7S,8R,13S,14S,15S)-8,14-bis(4-methoxybenzyloxy)-5,7,13,15-tetramethyl-20-(tetrahydropyran-2-yloxy)eicosa-1,3,11,16-tetraen-6-ol
  参考文献：
  名称：

  强大的微管稳定剂（+）-discodermolide的简化类似物的合成和生物学评估。

  摘要：

  有效，收敛和立体控制的有效抗有丝分裂剂（+）-discodermolide的简化类似物的合成已实现，并已准备了几个小库。在所有文库中，除去了C14和C16上的二脱甲基亚甲基和C7羟基，并用简单的酯代替了内酯。每个系列类似物中引入的其他修饰与天然产物的C11，C17和C19有关。合成策略的关键要素包括（a）从一个常见的中间体中精制主要亚基，以及（b）使用Wittig反应安装（Z）-烯烃的片段偶联。分析了文库组件的体外微管稳定作用，[3H]紫杉醇从其在微管蛋白上的结合位点的置换，通过基于多参数荧光细胞的筛选技术，它具有针对人类癌细胞的抗增殖活性，以及​​用于细胞信号传导和有丝分裂纺锤体改变。结果表明，即使明显的结构简化也可以导致类似物具有与微管靶向相关的作用。

  DOI：

  10.1016/s0968-0896(03)00186-x
• 作为产物：
  描述：

  (4R,5S,6S,7S)-1,6-bis(tert-butyldimethylsilanyloxy)-5,7-dimethylnon-8-en-4-ol 在 吡啶 、 咪唑 、 chromium dichloride 、 三氟甲磺酸 、 碘 、 sodium hydride 、 氟化氢吡啶 、 臭氧 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 苯 为溶剂， 反应 101.0h， 生成 (Z)-(5S,6S,7S,8R)-11-iodo-8-(4-methoxybenzyloxy)-5,7-dimethylundeca-1,3-dien-6-yl tert-butyldimethylsilyl ether
  参考文献：
  名称：

  强大的微管稳定剂（+）-discodermolide的简化类似物的合成和生物学评估。

  摘要：

  有效，收敛和立体控制的有效抗有丝分裂剂（+）-discodermolide的简化类似物的合成已实现，并已准备了几个小库。在所有文库中，除去了C14和C16上的二脱甲基亚甲基和C7羟基，并用简单的酯代替了内酯。每个系列类似物中引入的其他修饰与天然产物的C11，C17和C19有关。合成策略的关键要素包括（a）从一个常见的中间体中精制主要亚基，以及（b）使用Wittig反应安装（Z）-烯烃的片段偶联。分析了文库组件的体外微管稳定作用，[3H]紫杉醇从其在微管蛋白上的结合位点的置换，通过基于多参数荧光细胞的筛选技术，它具有针对人类癌细胞的抗增殖活性，以及​​用于细胞信号传导和有丝分裂纺锤体改变。结果表明，即使明显的结构简化也可以导致类似物具有与微管靶向相关的作用。

  DOI：

  10.1016/s0968-0896(03)00186-x

文献信息

• Discodermolide/Dictyostatin Hybrids:  Synthesis and Biological Evaluation
  作者：Youseung Shin、Nakyen Choy、Raghavan Balachandran、Charitha Madiraju、Billy W. Day、Dennis P. Curran

  DOI：10.1021/ol026942l

  日期：2002.12.1

  [structure: see text] Two hybrid analogues of discodermolide and dictyostatin (3, 26) have been designed and synthesized. These are the first macrocyclic analogues of discodermolide and biological activities were evaluated and compared with linear discodermolide analogues.

  [结构：见正文]已设计并合成了二编码器莫迪尔和双香豆素（3，26）的两个杂合类似物。这些是第一个discodermolide的大环类似物，并对其生物学活性进行了评估，并与线性discodermolide的类似物进行了比较。
• [EN] ANALOGS OF DISCODERMOLIDE AND DICTYOSTATIN-1, INTERMEDIATES THEREFOR AND METHODS OF SYNTHESIS THEREOF<br/>[FR] ANALOGUES DE DISCODERMOLIDE ET DE DICTYOSTATINE-1, INTERMEDIAIRES CORRESPONDANTS, ET PROCEDES DE SYNTHESE CORRESPONDANTS
  申请人：UNIV PITTSBURGH

  公开号：WO2004022552A1

  公开（公告）日：2004-03-18

  A compound of the following structure: wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, an alkyl group, an aryl group, a benzyl group, a trityl group, -SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, -RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or -NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 is (CH2)n where n is and integer in the range of 0 to 5, -CH2CH(CH3)-, -CH=CH-, -CH=C(CH3)-, or -C=-C-; R4 is (CH2)p where p is an integer in the range of 4 to 12, -(CHRkl)yl (CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5C(Rsl )=C(Rs2)C(Rs3)=C(Rs4)-, -(CHRk1 )yl (CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5CH(Rs I)CH(Rs2)C(Rs3)=C(Rs4)-, -(CHRk1)yl (CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRks)y5C(Rsl)=C(Rs2)CH(Rs3)CH(Rs4)-, -(CHRkI )yl (CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5CH(Rsl)CH(Rs2)CH(Rs3)CH(R s4)-, wherein y1 and y2 are 1 and y3, y4 and y5 are independently 0 or 1, Rk1, Rk2, Rk3, Rk4 and Rk5 are independently H, CH3, or OR2a, and Rs1, Rs2, Rs3, and Rs4 are independently H or CH3, wherein R2a is H, an alkyl group, an aryl group, a benzyl group, a trityl group, -SiRaRbRc, CH2ORd, or CORe; and R5 is H or OR2b, wherein R2b is H, an alkyl group, an aryl group, an aryl group, a benzyl group, a trityl group, -SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.

  以下是该结构的化合物：其中R1为H、烷基基团、芳基、烯基基团、炔基基团或卤素原子；R2为H、烷基基团、芳基、苄基、三苄基、-SiRaRbRc、 ORd或CORe；Ra、Rb和Rc独立地为烷基基团或芳基；Rd为烷基基团、芳基、烷氧基烷基团、-RiSiRaRbRc或苄基，其中Ri为烷基烷基团；Re为烷基基团、烯丙基基团、苄基、芳基、烷氧基或-NRgRh，其中Rg和Rh独立地为H、烷基基团或芳基；R3为(CH2)n，其中n为0到5范围内的整数，- CH(CH3)-、-CH=CH-、-CH=C( )-或-C=-C-；R4为( )p，其中p为4到12范围内的整数，-(CHRkl)yl (CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5C(Rsl )=C(Rs2)C(Rs3)=C(Rs4)-、-(CHRk1 )yl (CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5CH(Rs I)CH(Rs2)C(Rs3)=C(Rs4)-、-(CHRk1)yl (CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRks)y5C(Rsl)=C(Rs2)CH(Rs3)CH(Rs4)-、-(CHRkI )yl (CHRk2)y2(CHRk3)y3(CHRk4)y4(CHRk5)y5CH(Rsl)CH(Rs2)CH(Rs3)CH(R s4)-，其中y1和y2为1，y3、y4和y5独立地为0或1，Rk1、Rk2、Rk3、Rk4和Rk5独立地为H、 或OR2a，Rs1、Rs2、Rs3和Rs4独立地为H或 ，其中R2a为H、烷基基团、芳基、苄基、三苄基、-SiRaRbRc、 ORd或CORe；R5为H或OR2b，其中R2b为H、烷基基团、芳基、芳基、苄基、三苄基、-SiRaRbRc、 ORd或CORe；前提是该化合物不是dictyostatin 1。
• Simplified Discodermolide Analogues:  Synthesis and Biological Evaluation of 4-<i>e</i><i>pi</i>-7-Dehydroxy-14,16-didemethyl-(+)-discodermolides as Microtubule-Stabilizing Agents
  作者：Nakyen Choy、Youseung Shin、Phu Qui Nguyen、Dennis P. Curran、Raghavan Balachandran、Charitha Madiraju、Billy W. Day

  DOI：10.1021/jm0204136

  日期：2003.7.1

  Several novel analogues of (+)-discodermolide were synthesized via a convergent strategy that used Wittig reactions to append left and right side chains to a central scaffold and then tested for biological activity. Three of the analogues in the 4-epi-7-dehydroxy-14,16-didemethyl series, 6a-c, had interesting actions. The C3-methoxymethyl ether analogue 6b was more active in antiproliferative cell-based assays as well as in hypernucleation and paclitaxel site competition assays with isolated tubulin than the other analogues, including 6a, which contained a free hydroxyl group at the C3 position. The biological results validated the initial hypothesis that the C7 hydroxy group and the C14 and C16 methyl groups of (+)-discodermolide could be deleted without undermining activity. Although less potent than (+)-discodermolide and paclitaxel, compounds 6b and 6c both showed properties unique to (+)-discodermolide. These properties, particularly the capacity to cause hypernucleation of isolated tubulin at lower temperature than paclitaxel, as well as stabilizing preformed microtubules to cold disassembly, are considered mechanistically superior to those of paclitaxel. Other variations in the right and left sides of the discodermolide scaffold revealed additional structure/activity information.