(4R)-6-[tert-buty(dimethyl)silyloxy]-4-methyl-2-methylidenehexanal | 1422462-87-0

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (4R)-6-[tert-buty(dimethyl)silyloxy]-4-methyl-2-methylidenehexanal
• 英文别名: (4R)-6-[tert-butyl(dimethyl)silyl]oxy-4-methyl-2-methylidenehexanal
• CAS: 1422462-87-0
• 化学式: C₁₄H₂₈O₂Si
• 分子量: 256.461
• InChiKey: DHGSJEGKQOKPKJ-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4R)-6-[tert-buty(dimethyl)silyloxy]-4-methyl-2-methylidenehexanal 在 吡啶 、 titanium(IV) isopropylate 、 甲醇 、 叔丁基过氧化氢 、 4-二甲氨基吡啶 、 ammonium hydroxide 、 四丙基高钌酸铵 、 barium hydroxide octahydrate 、 L-(+)-酒石酸二异丙酯 、 三丁基膦 、 双(三甲基硅基)过氧化物 、 dimethyl sulfide borane 、 2,4,6-三氯苯甲酰氯 、 camphor-10-sulfonic acid 、 三(二甲氨基)锍二氟三甲基硅酸 、 水 、 sodium hydride 、 二异丁基氢化铝 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙胺 、 红铝 、 (S)-2-甲基-CBS-恶唑硼烷 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 癸烷 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 92.33h， 生成 (1R,2E,6E,10S,12R,13S,14R,17S,19R,20E,24R,26R)-13,14,17,19-tetrahydroxy-7,10,12,19,20,24-hexamethyl-22-methylidene-9,27-dioxabicyclo[24.1.0]heptacosa-2,6,20-triene-8,15-dione
  参考文献：
  名称：

  Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation

  摘要：

  The total syntheses of amphidinolide B-1 and the proposed structure of amphidinolide B-2 have been accomplished. Key aspects of this work include the development of a practical, non-transitionmetal-mediated method for the construction of the C-13-C-15 diene, the identification of alpha-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B-2 and diastereomers thereof display potent antitumor activities with IC50 values ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B-2 is over 12-fold more potent than the C-8,C-9-epimer and C-18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.

  DOI：

  10.1021/jo3026077
• 作为产物：
  描述：

  (3R)-5-[(4-methoxyphenyl)methoxymethyl]-3-methylhex-5-enal 在 咪唑 、 二异丁基氢化铝 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (4R)-6-[tert-buty(dimethyl)silyloxy]-4-methyl-2-methylidenehexanal
  参考文献：
  名称：

  Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation

  摘要：

  The total syntheses of amphidinolide B-1 and the proposed structure of amphidinolide B-2 have been accomplished. Key aspects of this work include the development of a practical, non-transitionmetal-mediated method for the construction of the C-13-C-15 diene, the identification of alpha-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B-2 and diastereomers thereof display potent antitumor activities with IC50 values ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B-2 is over 12-fold more potent than the C-8,C-9-epimer and C-18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.

  DOI：

  10.1021/jo3026077

文献信息

• New 2-substituted functionalized allyl halides in the synthesis of fragments of amphidinolides B, D, G, H, and L
  作者：I. V. Mineeva

  DOI：10.1134/s1070428017030204

  日期：2017.3

  asymmetric syntheses of several new allyl bromides as C9–C14 fragments of cytotoxic macrolactones, amphidinolides B, D, G, H, and L, have been developed starting from accessible 1-[(2S)-4,4-dimethoxy-2-methylbutyl]cyclopropyl methanesulfonate prepared through cyclopropanol intermediates. Original synthetic approaches to the C7–C16, C7–C14, and C9–C16 amphidinolide fragments are also described.

  从有效的1-[（2 S）-4,4开始，开发了几种新的烯丙基溴的简单有效的不对称合成物，作为细胞毒性大内酯，两性霉素B，D，G，H和L的C 9 –C 14片段。通过环丙醇中间体制得-二甲氧基-2-甲基丁基]环丙基甲磺酸酯。还描述了对C 7 -C 16，C 7 -C 14和C 9 -C 16苯二环内酯片段的原始合成方法。
• Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation
  作者：Liang Lu、Wei Zhang、Sangkil Nam、David A. Horne、Richard Jove、Rich G. Carter

  DOI：10.1021/jo3026077

  日期：2013.3.15

  The total syntheses of amphidinolide B-1 and the proposed structure of amphidinolide B-2 have been accomplished. Key aspects of this work include the development of a practical, non-transitionmetal-mediated method for the construction of the C-13-C-15 diene, the identification of alpha-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B-2 and diastereomers thereof display potent antitumor activities with IC50 values ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B-2 is over 12-fold more potent than the C-8,C-9-epimer and C-18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.