[5-(tert-butyl-diphenyl-silanyloxy)-3,3-dimethyl-tetrahydro-2,4-dioxa-cyclopropa[α]pentalen-1α-yl]-methanol | 1215320-15-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [5-(tert-butyl-diphenyl-silanyloxy)-3,3-dimethyl-tetrahydro-2,4-dioxa-cyclopropa[α]pentalen-1α-yl]-methanol
• 英文别名: [(1R,2R,4S,5S,6R)-5-[tert-butyl(diphenyl)silyl]oxy-8,8-dimethyl-7,9-dioxatricyclo[4.3.0.02,4]nonan-2-yl]methanol
• CAS: 1215320-15-2
• 化学式: C₂₆H₃₄O₄Si
• 分子量: 438.639
• InChiKey: HORVTZVFDYVNOM-SQSAXNKISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [5-(tert-butyl-diphenyl-silanyloxy)-3,3-dimethyl-tetrahydro-2,4-dioxa-cyclopropa[α]pentalen-1α-yl]-methanol 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以73%的产率得到(1R,2S,4S,5S,6R)-5-[tert-butyl(diphenyl)silyl]oxy-8,8-dimethyl-7,9-dioxatricyclo[4.3.0.02,4]nonane-2-carbaldehyde
  参考文献：
  名称：

  Structure−Activity Relationship of (N)-Methanocarba Phosphonate Analogues of 5′-AMP as Cardioprotective Agents Acting Through a Cardiac P2X Receptor

  摘要：

  P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (genetic model of heart failure) compared to vehicle-infused mice (all inactive at the vasodilatory P2Y(1) receptor). Two phosphonates, (1'S,2'R,3',5,4'R,5'S)-4'-(6-amino-2-chloropurin-9-y1)-2',3'-(dihydroxy)-1'-(phosphonomethylene)-bicyclo[3.1.0]hexane, 4 (MRS2775), and its homologue 9 (MRS2935), both 5'-saturated, containing a 2-Cl substitution, improved echocardiography-derived fractional shortening (20.25% and 19.26%, respectively, versus 13.78% in controls), while unsaturated 5'-extended phosphonates, all 2-H analogues, and a CH3-phosphonate were inactive. Thus, chronic administration of nucleotidase-resistant phosphonates conferred a beneficial effect, likely via cardiac P2X receptor activation. Thus, we have greatly expanded the range of carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure.

  DOI：

  10.1021/jm9018542
• 作为产物：
  描述：

  5-(tert-butyl-diphenyl-silanyloxy)-3,3-dimethyl-tetrahydro-2,4-dioxa-cyclopropa[α]pentalene-1α-carboxylic acid ethyl ester 在 二异丁基氢化铝 、 甲醇 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 2.5h， 以54%的产率得到[5-(tert-butyl-diphenyl-silanyloxy)-3,3-dimethyl-tetrahydro-2,4-dioxa-cyclopropa[α]pentalen-1α-yl]-methanol
  参考文献：
  名称：

  P2Y14 受体的分子识别：探索尿苷-5'-二磷酸葡萄糖的结构许可末端糖部分

  摘要：

  P2Y 14受体是一种核苷酸信号蛋白，由尿苷-5'-二磷酸葡萄糖1和其他尿嘧啶核苷酸激活。我们已经确定1的葡萄糖部分是设计该 P2Y 14激动剂类似物的最结构允许区域。例如，尿苷-5'-二磷酸葡萄糖醛酸的羧酸酯基团被证明适用于通过酰胺键进行链延伸的灵活取代。通过该策略制备的含有末端 2-酰基氨基乙基酰胺的功能化同源物保留了 P2Y 14活性，分子模型预测该链与受体的第二个细胞外环非常接近。此外，用其他糖替代葡萄糖不会降低 P2Y 14效力。例如，[5'']核糖衍生物的EC 50为0.24 μM。的葡萄糖部分的选择性monofluorination指示用于2'角色' -和6'' -的羟基1受体识别。β-葡萄糖苷的效力比天然 α-异构体低两倍，但 1''-氧的亚甲基替代消除了活性。用环戊基或刚性双环 [3.1.0] 己烷基团取代核糖环系统消除了活性。Uridine-5'-diphosphoglucose

  DOI：

  10.1016/j.bmc.2009.05.024

文献信息

• Molecular recognition in the P2Y14 receptor: Probing the structurally permissive terminal sugar moiety of uridine-5′-diphosphoglucose
  作者：Hyojin Ko、Arijit Das、Rhonda L. Carter、Ingrid P. Fricks、Yixing Zhou、Andrei A. Ivanov、Artem Melman、Bhalchandra V. Joshi、Pavol Kováč、Jan Hajduch、Kenneth L. Kirk、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1016/j.bmc.2009.05.024

  日期：2009.7

  substitution by chain extension through an amide linkage. Functionalized congeners containing terminal 2-acylaminoethylamides prepared by this strategy retained P2Y14 activity, and molecular modeling predicted close proximity of this chain to the second extracellular loop of the receptor. In addition, replacement of glucose with other sugars did not diminish P2Y14 potency. For example, the [5′′]ribose derivative

  P2Y 14受体是一种核苷酸信号蛋白，由尿苷-5'-二磷酸葡萄糖1和其他尿嘧啶核苷酸激活。我们已经确定1的葡萄糖部分是设计该 P2Y 14激动剂类似物的最结构允许区域。例如，尿苷-5'-二磷酸葡萄糖醛酸的羧酸酯基团被证明适用于通过酰胺键进行链延伸的灵活取代。通过该策略制备的含有末端 2-酰基氨基乙基酰胺的功能化同源物保留了 P2Y 14活性，分子模型预测该链与受体的第二个细胞外环非常接近。此外，用其他糖替代葡萄糖不会降低 P2Y 14效力。例如，[5'']核糖衍生物的EC 50为0.24 μM。的葡萄糖部分的选择性monofluorination指示用于2'角色' -和6'' -的羟基1受体识别。β-葡萄糖苷的效力比天然 α-异构体低两倍，但 1''-氧的亚甲基替代消除了活性。用环戊基或刚性双环 [3.1.0] 己烷基团取代核糖环系统消除了活性。Uridine-5'-diphosphoglucose
• Structure−Activity Relationship of (<i>N</i>)-Methanocarba Phosphonate Analogues of 5′-AMP as Cardioprotective Agents Acting Through a Cardiac P2X Receptor
  作者：T. Santhosh Kumar、Si-Yuan Zhou、Bhalchandra V. Joshi、Ramachandran Balasubramanian、Tiehong Yang、Bruce T. Liang、Kenneth A. Jacobson

  DOI：10.1021/jm9018542

  日期：2010.3.25

  P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (genetic model of heart failure) compared to vehicle-infused mice (all inactive at the vasodilatory P2Y(1) receptor). Two phosphonates, (1'S,2'R,3',5,4'R,5'S)-4'-(6-amino-2-chloropurin-9-y1)-2',3'-(dihydroxy)-1'-(phosphonomethylene)-bicyclo[3.1.0]hexane, 4 (MRS2775), and its homologue 9 (MRS2935), both 5'-saturated, containing a 2-Cl substitution, improved echocardiography-derived fractional shortening (20.25% and 19.26%, respectively, versus 13.78% in controls), while unsaturated 5'-extended phosphonates, all 2-H analogues, and a CH3-phosphonate were inactive. Thus, chronic administration of nucleotidase-resistant phosphonates conferred a beneficial effect, likely via cardiac P2X receptor activation. Thus, we have greatly expanded the range of carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure.