(4R)-4-benzyl-3-[(2R,3S,4R,5S)-5-(tert-butyldimethylsilanyloxy)-8-(4-methoxybenzyloxy)-3-methoxymethoxy-2,4-dimethyloctanoyl]oxazolidin-2-one | 565229-03-0

• 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: (4R)-4-benzyl-3-[(2R,3S,4R,5S)-5-(tert-butyldimethylsilanyloxy)-8-(4-methoxybenzyloxy)-3-methoxymethoxy-2,4-dimethyloctanoyl]oxazolidin-2-one
• 英文别名: (4R)-4-benzyl-3-[(2R,3S,4S,5S)-5-[tert-butyl(dimethyl)silyl]oxy-3-(methoxymethoxy)-8-[(4-methoxyphenyl)methoxy]-2,4-dimethyloctanoyl]-1,3-oxazolidin-2-one
• CAS: 565229-03-0
• 化学式: C₃₆H₅₅NO₈Si
• 分子量: 657.92
• InChiKey: WORNJEYGMQRZSG-HXUACRRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.23
• 重原子数：
  46
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  92.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4R)-4-benzyl-3-[(2R,3S,4R,5S)-5-(tert-butyldimethylsilanyloxy)-8-(4-methoxybenzyloxy)-3-methoxymethoxy-2,4-dimethyloctanoyl]oxazolidin-2-one 在 氟化氢吡啶 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 48.0h， 以83%的产率得到6-[(3R,4S,5S,6S)-3-(4-methoxybenzyloxy)propyl]-4-methoxymethoxy-3,5-dimethyltetrahydropyran-2-one
  参考文献：
  名称：

  [EN] ANALOGS OF DISCODERMOLIDE AND DICTYOSTATIN-1, INTERMEDIATES THEREFOR AND METHODS OF SYNTHESIS THEREOF
  [FR] ANALOGUES DE DISCODERMOLIDE ET DE DICTYOSTATINE-1, INTERMEDIAIRES CORRESPONDANTS, ET PROCEDES DE SYNTHESE CORRESPONDANTS

  摘要：

  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、CH2ORd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，-CH2CH(CH3)-、-CH=CH-、-CH=C(CH3)-或-C=-C-；R4为(CH2)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、CH3或OR2a，Rs1、Rs2、Rs3和Rs4独立地为H或CH3，其中R2a为H、烷基基团、芳基、苄基、三苄基、-SiRaRbRc、CH2ORd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、CH2ORd或CORe；前提是该化合物不是dictyostatin 1。

  公开号：

  WO2004022552A1
• 作为产物：
  描述：

  4-[(4-甲氧基苯基)甲氧基]丁醛 在 2,6-二甲基吡啶 、 锂硼氢 、 三氟甲磺酸二丁硼 、 三氧化硫吡啶 、 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 13.67h， 生成 (4R)-4-benzyl-3-[(2R,3S,4R,5S)-5-(tert-butyldimethylsilanyloxy)-8-(4-methoxybenzyloxy)-3-methoxymethoxy-2,4-dimethyloctanoyl]oxazolidin-2-one
  参考文献：
  名称：

  Simplified Discodermolide Analogues:  Synthesis and Biological Evaluation of 4-epi-7-Dehydroxy-14,16-didemethyl-(+)-discodermolides as Microtubule-Stabilizing Agents

  摘要：

  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.

  DOI：

  10.1021/jm0204136