(3S,4S,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne-2-yl trifluoromethanesulfonate | 1207734-97-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: (3S,4S,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne-2-yl trifluoromethanesulfonate
• 英文别名: [(3S,4S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-4-methyloct-1-en-7-yn-2-yl] trifluoromethanesulfonate
• CAS: 1207734-97-1
• 化学式: C₂₂H₄₁F₃O₅SSi₂
• 分子量: 530.797
• InChiKey: UOCNJKUITKASQK-UHOSZYNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.81
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3S,4S,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne-2-yl trifluoromethanesulfonate 、 8E-bromomethylene-(20S,23R)-epoxymethano-25-[triethylsilyloxy]-des-A,B-cholestan-8-one 在 叔丁基锂 、 zinc dibromide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 反应 6.1h， 生成 [(1R,2S,3S,5Z)-5-[(2E)-2-[(1S,3aS,7aS)-7a-methyl-1-[(2S,4S)-2-methyl-4-(2-methyl-2-triethylsilyloxypropyl)oxolan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-3-[tert-butyl(dimethyl)silyl]oxy-2-methyl-4-methylidenecyclohexyl]oxy-tert-butyl-dimethylsilane
  参考文献：
  名称：

  Structure−Function Relationships and Crystal Structures of the Vitamin D Receptor Bound 2α-Methyl-(20S,23S)- and 2α-Methyl-(20S,23R)-epoxymethano-1α,25-dihydroxyvitamin D₃

  摘要：

  The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1 alpha,25(OH)(2)D-3 analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. We recently showed that the synthetic analogue (20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (2a) acts as a 1 alpha,25(OH)(2)D-3 superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1 alpha,25(OH)(2)D-3,2 alpha-methyl-1 alpha,25(OH)(2)D-3, or 2a, we designed a novel analogue, 2 alpha-methyl-(20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.

  DOI：

  10.1021/jm9014636
• 作为产物：
  描述：

  (3S,4S,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-8,8-dibromo-4-methyloct-7-en-2-one 、 2-[N,正双(三氟甲烷烷磺酰)氨基]-5-氯吡啶 在 lithium diisopropyl amide 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 12.25h， 以75%的产率得到(3S,4S,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne-2-yl trifluoromethanesulfonate
  参考文献：
  名称：

  Structure−Function Relationships and Crystal Structures of the Vitamin D Receptor Bound 2α-Methyl-(20S,23S)- and 2α-Methyl-(20S,23R)-epoxymethano-1α,25-dihydroxyvitamin D₃

  摘要：

  The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1 alpha,25(OH)(2)D-3 analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. We recently showed that the synthetic analogue (20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (2a) acts as a 1 alpha,25(OH)(2)D-3 superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1 alpha,25(OH)(2)D-3,2 alpha-methyl-1 alpha,25(OH)(2)D-3, or 2a, we designed a novel analogue, 2 alpha-methyl-(20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.

  DOI：

  10.1021/jm9014636

文献信息

• An Expeditious Route to 1α,25-Dihydroxyvitamin D₃and Its Analogues by an Aqueous Tandem Palladium-Catalyzed A-Ring Closure and Suzuki Coupling to the C/D Unit
  作者：Pranjal Gogoi、Rita Sigüeiro、Silvina Eduardo、Antonio Mouriño

  DOI：10.1002/chem.200902972

  日期：2010.2.1

  mild, general, and highly stereoselective Pd0‐catalyzed cascade to the triene system of the hormone 1α,25‐dihydroxyvitamin D3 and six representative analogues is reported. The intramolecular cyclization of an enol–triflate (lower fragment) followed in situ by Suzuki–Miyaura coupling with an alkenyl boronic ester (upper fragment, also efficiently prepared by Pd0‐catalyzed coupling) in equimolar amounts

  每日维生素：有轻度，一般和高度立体选择性的Pd 0催化与1α，25-二羟基维生素D 3和6种代表性类似物的三烯系统级联。在质子化条件下等摩尔量的烯醇-三氟甲磺酸分子的分子内环化（下片段），然后是铃木-宫浦（Suzuki-Miyaura）与烯基硼酸酯（上片段，也可通过Pd 0催化偶联有效制备）原位合成用于生物测试的少量新维生素D类似物（请参阅计划）。
• Structure−Function Relationships and Crystal Structures of the Vitamin D Receptor Bound 2α-Methyl-(20<i>S</i>,23<i>S</i>)- and 2α-Methyl-(20<i>S</i>,23<i>R</i>)-epoxymethano-1α,25-dihydroxyvitamin D₃
  作者：Pierre Antony、Rita Sigüeiro、Tiphaine Huet、Yoshiteru Sato、Nick Ramalanjaona、Luis Cezar Rodrigues、Antonio Mouriño、Dino Moras、Natacha Rochel

  DOI：10.1021/jm9014636

  日期：2010.2.11

  The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1 alpha,25(OH)(2)D-3 analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. We recently showed that the synthetic analogue (20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (2a) acts as a 1 alpha,25(OH)(2)D-3 superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1 alpha,25(OH)(2)D-3,2 alpha-methyl-1 alpha,25(OH)(2)D-3, or 2a, we designed a novel analogue, 2 alpha-methyl-(20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.