(1S,2R,4S,5R)-5[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-4-hydroxybicyclo[3.1.0]hex-2-yl benzoate | 452335-28-3

• 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: (1S,2R,4S,5R)-5[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-4-hydroxybicyclo[3.1.0]hex-2-yl benzoate
• 英文别名: [(1S,2R,4S,5R)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-4-hydroxy-2-bicyclo[3.1.0]hexanyl] benzoate
• CAS: 452335-28-3
• 化学式: C₃₀H₃₄O₄Si
• 分子量: 486.683
• InChiKey: KWHIVGVORVCMTK-KWWFCQITSA-N

物化性质

• 沸点：
  555.4±46.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.56
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2R,4S,5R)-5[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-4-hydroxybicyclo[3.1.0]hex-2-yl benzoate 在 碘 、 sodium methylate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 生成 (1'S,2'S,5'R)-1-{5-[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]bicyclo[3.1.0]hex-3-en-2-yl}-5-methyl-3-(phenylcarbonyl)-1,3-dihydropyrimidine-2,4-dione
  参考文献：
  名称：

  Recent Advances in the Synthesis of Conformationally Locked Nucleosides and Their Success in Probing the Critical Question of Conformational Preferences by Their Biological Targets

  摘要：

  The present work describes some recent approaches to the syntheses of three classes of locked-North nucleosides: beta-D-ribo-, beta-D-deoxyribo-, and beta-D-dideoxy-ribonucleosides. The method developed for the latter class permitted access to a novel bicyclo[3.1.0]hexene-type nucleosides structurally similar to D4T and carbovir. A structural analysis and biological activities are discussed.

  DOI：

  10.1081/ncn-120021954
• 作为产物：
  描述：

  (1S,2R,4S,5R)-4-(phenylmethoxy)-5-[(phenylmethoxy)methyl]bicyclo[3.1.0]hexan-2-ol 在 钯 吡啶 、 咪唑 、 甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 (1S,2R,4S,5R)-5[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-4-hydroxybicyclo[3.1.0]hex-2-yl benzoate
  参考文献：
  名称：

  A Conformationally Locked Analogue of the Anti-HIV Agent Stavudine. An Important Correlation between Pseudorotation and Maximum Amplitude

  摘要：

  The synthesis and biological evaluation of a bicyclo[3.1.0]hexene nucleoside designed as a conformational mimic of the anti-HIV agent stavudine (1, D4T) is described. The unsaturated methanocarbocyclic pseudosugar of N-MCD4T (2) was constructed from an iodo-substituted precursor by a DBU-catalyzed olefination reaction. Mitsunobu coupling with N-3-benzoylthymine afforded the desired target after deprotection. Both D4T and N-MCD4T are in the North (N) hemisphere of the pseudorotational cycle but 70degrees away from a perfect N (P = 0degrees) conformation toward the East and West hemispheres, respectively. Despite this large difference, the double bond reduces the puckering amplitude (v(max)) of N-MCD4T to 6.81degrees, and the superposition of both structures showed a RMS deviation of only 0.039 Angstrom. The combined structural analysis of P and vmax shows that while the value of P may differ substantially, the low v(max) resolves the differences and becomes the dominant pseudorotational. parameter. N-MCD4T is active against HIV-1 and HIV-2 in CEM, MT-2, and MT-4 cells, and while it is somewhat less potent than D4T, it also appears to be less toxic. The triphosphate (N-MCD4TTP) inhibits HIV reverse transcriptase with a 10-fold higher IC50 than D4TTP. By virtue of its carbocyclic nature, N-MCD4T (2) is a more robust molecule stable to conditions that would cleave D4T.

  DOI：

  10.1021/jm030116g

文献信息

• Enantioselective Synthesis of Bicyclo[3.1.0]hexane Carbocyclic Nucleosides via a Lipase-Catalyzed Asymmetric Acetylation. Characterization of an Unusual Acetal Byproduct
  作者：Yuichi Yoshimura、Hyung R. Moon、Yongseok Choi、Victor E. Marquez

  DOI：10.1021/jo020249u

  日期：2002.8.1

  The bicyclo[3.1.0]hexane scaffold can lock the conformation of a carbocyclic nucleoside into one of the two antipodal (north or south) conformations typical of conventional nucleosides that normally exist in a rapid, two-state equilibrium in solution. In a recent brief communication, we reported a practical method to access the requisite bicyclo[3.1.0]hexane pseudosugar for the north antipode via an

  双环[3.1.0]己烷骨架可将碳环核苷的构型锁定为通常在溶液中以快速，两态平衡存在的常规核苷典型的两个对映体（北或南）构型之一。在最近的简短交流中，我们报道了一种通过分子内烯烃-酮卡宾环加成反应获得对映体所需的双环[3.1.0]己烷假糖的实用方法。该合成法最吸引人的特征是，可以从简单且廉价的起始原料中获得相对复杂的合成子，并且嘌呤核苷的外消旋混合物可以通过腺苷脱氨酶（ADA）水解成功分离。在这项工作中，我们描述了一种更普遍的脂肪酶催化双乙酰化反应的发展，可以成功地将较早的前体4-（叔丁基二苯基硅甲氧基）-1-（羟甲基）双环[3.1.0]己-2-醇[（+/-）-7]拆分为对映体纯的（+）-二乙酸酯8和（-）-单乙酸酯9。原来的双乙酸酯被转化为构象锁定的（北）-碳环鸟苷（+）-17，与先前通过ADA解析得到的相同。本方法代表了适用于合成所有类型的（北）双环[3.1.0]己烷核苷，包括嘧啶类似物