tert-butyldimethyl[(2-methyloxiran-2-yl)methoxy]silane | 147220-50-6

• 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: tert-butyldimethyl[(2-methyloxiran-2-yl)methoxy]silane
• 英文别名: tert-butyl-dimethyl-[(2-methyloxiran-2-yl)methoxy]silane
• CAS: 147220-50-6
• 化学式: C₁₀H₂₂O₂Si
• 分子量: 202.369
• InChiKey: YRWBWBRTFFYLTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyldimethyl[(2-methyloxiran-2-yl)methoxy]silane 在 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 23.0h， 生成 1-{3-[(tert-butyldimethylsilyl)oxy]-2-methyl-2-[(tetrahydro-2H-pyran-2-yl)oxy]propyl}-2,4-dinitro-1H-imidazole
  参考文献：
  名称：

  Development of (6R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis

  摘要：

  Discovery of the potent antileishmanial effects of antitubercular 6-nitro-2,3-dihydroimidazo [2,1-1)] [1,3]oxazoles and 7-substituted 2-nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazines stimulated the examination of further scaffolds (e.g., 2-nitro-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]oxazepines), but the results for these seemed less attractive. Following the screening of a 900-compound pretomanid analogue library, several hits with more suitable potency, solubility, and microsomal stability were identified, and the superior efficacy of newly synthesized 6R enantiomers with phenylpyridine-based side chains was established through head-to-head assessments in a Leishmania donovani mouse model. Two such leads (R-84 and R-89) displayed promising activity in the more stringent Leishmania infantum hamster model but were unexpectedly found to be potent inhibitors of hERG. An extensive structure-activity relationship investigation pinpointed two compounds (R-6 and pyridine R-136) with better solubility and pharmacokinetic properties that also provided excellent oral efficacy in the same hamster model (>97% parasite clearance at 25 mg/kg, twice daily) and exhibited minimal hERG inhibition. Additional profiling earmarked R-6 as the favored backup development candidate.

  DOI：

  10.1021/acs.jmedchem.7b01581
• 作为产物：
  描述：

  tert-butyldimethyl(2-methylallyloxy)silane 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到tert-butyldimethyl[(2-methyloxiran-2-yl)methoxy]silane
  参考文献：
  名称：

  2,2-二取代环氧化物的区域选择性羰基化：酮基羟醛产品的替代途径

  摘要：

  我们报告了 2,2-二取代环氧化物到 β,β-二取代 β-内酯的区域选择性羰基化。机理研究表明，环氧化物开环是周转限制步骤，这一见解有助于使用弱供体的醚溶剂开发改进的反应条件。广泛的环氧化物可以羰基化为 β-内酯，随后开环产生基于酮的醛醇加合物，为 Mukaiyama 醛醇反应提供替代方案。对映纯的环氧化物被证明经过羰基化/开环过程并保留立体化学以形成对映纯的 β-羟基酯。

  DOI：

  10.1021/jacs.8b12286

文献信息

• Enantioselective Hydrolysis of Functionalized 2,2-Disubstituted Oxiranes with Bacterial Epoxide Hydrolases
  作者：Andreas Steinreiber、Ingrid Osprian、Sandra F. Mayer、Romano V. A. Orru、Kurt Faber

  DOI：10.1002/1099-0690(200011)2000:22<3703::aid-ejoc3703>3.0.co;2-3

  日期：2000.11

  ether-oxygen to the stereogenic quaternary carbon center of the oxirane ring had a profound influence on the enantioselectivity, and several oxiranes were resolved with good to excellent selectivities. The enantiomerically enriched epoxides and vicinal diols thus obtained contain a useful “synthetic handle” in their side chain, which allows their use as building blocks in asymmetric synthesis.

  使用 11 种细菌菌株的环氧化物水解酶活性研究了带有各种氧官能团的 2,2-二取代环氧乙烷的生物水解。结果表明，活性和选择性强烈依赖于底物结构和生物催化剂。尽管具有游离羟基的底物没有被转化，但它们的类似物，被保护为醚，被广泛接受。这使得通过根据尺寸和极性正确选择醚组，可以方便地调制对映射性。发现醚-氧与环氧乙烷环的立体四元碳中心的距离对对映选择性有深远的影响，并且几种环氧乙烷以良好到极好的选择性分离。
• 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]thiazoles: Facile synthesis and comparative appraisal against tuberculosis and neglected tropical diseases
  作者：Andrew M. Thompson、Adrian Blaser、Brian D. Palmer、Robert F. Anderson、Sujata S. Shinde、Delphine Launay、Eric Chatelain、Louis Maes、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、William A. Denny

  DOI：10.1016/j.bmcl.2017.03.069

  日期：2017.6

  its assessment in an acute Mycobacterium tuberculosis mouse model, alongside the corresponding oxazole (48), but the latter proved to be more efficacious. In vitro screening against kinetoplastid diseases revealed that nitroimidazothiazoles were inactive versus leishmaniasis but showed interesting activity, superior to that of the nitroimidazooxazoles, against Chagas disease. Overall, "thio-delamanid"

  为了寻求抗结核药物类前驱体（PA-824）的备份，我们研究了未开发的6-硝基-2,3-二氢咪唑并[2,1-b] [1,3]-噻唑和相关的-恶唑。硝基咪唑并噻唑是由2-溴-4-硝基咪唑通过与取代的噻喃和二异丙基乙胺加热而高产率制备的。这两个结构类别的等效实例提供了可广泛比较的MIC，其中2-甲基取代和优选的芳氧基甲基侧链扩展；尽管，S-氧化的噻唑类药物对结核病无效。联苯噻唑的有利的微粒体稳定性数据（45）与相应的恶唑（48）一起在急性结核分枝杆菌小鼠模型中进行了评估，但事实证明后者更为有效。体外对动素体疾病的筛选显示，硝基咪唑并噻唑对利什曼病无活性，但对查加斯病表现出有趣的活性，优于硝基咪唑并恶唑。总体而言，“硫磺-德拉曼尼德”（49）被认为是最佳的铅。
• [EN] SYSTEMS AND METHODS FOR REGIOSELECTIVE CARBONYLATION OF 2,2-DISUBSTITUTED EPOXIDES<br/>[FR] SYSTÈMES ET PROCÉDÉS DE CARBONYLATION RÉGIOSÉLECTIVE D'ÉPOXYDES 2,2-DISUBSTITUÉS
  申请人：UNIV CORNELL

  公开号：WO2020102816A1

  公开（公告）日：2020-05-22

  Provided are methods of carbonylating cyclic substrates to produce carbonyl ated cyclic products. The cyclic substrates may be 2, 2-di substituted epoxides and the cyclic products may be β,β-di substituted lactones. The method may be carried out by forming and pressurizing a reaction mixture of the cyclic substrate, a solvent, carbon monoxide, and a [LA+][CO(CO)4-] catalyst, where [LA+] is a Lewis acid capable of coordinating to the cyclic substrate. The method may proceed with a regioselectivity of 90:10 or greater. The resulting carbonylated cyclic products may be converted to ketone aldol products that retain the stereochemistry and enantiomeric ratio of the carbonyl ated cyclic products.

  提供了一种将环状底物羰基化以产生羰基化环状产物的方法。环状底物可以是2,2-二取代环氧化物，环状产物可以是β,β-二取代内酯。该方法可以通过形成并加压环状底物、溶剂、一氧化碳和[LA+][CO(CO)4-]催化剂的反应混合物来进行，其中[LA+]是能够与环状底物配位的路易斯酸。该方法可能以90:10或更高的区域选择性进行。所得的羰基化环状产物可以转化为保留羰基化环状产物的立体化学和对映比的酮醇产物。
• Organozirconocenes in organic synthesis: tandem epoxide rearrangement-carbonyl addition
  作者：Peter Wipf、Wenjing Xu

  DOI：10.1021/jo00056a011

  日期：1993.2

  Addition of catalytic amounts of AgClO4 to a mixture of organozirconocenes and epoxides results in the rapid formation of chain-extended secondary alcohols.
• Regioselective Carbonylation of 2,2-Disubstituted Epoxides: An Alternative Route to Ketone-Based Aldol Products
  作者：Aran K. Hubbell、Anne M. LaPointe、Jessica R. Lamb、Geoffrey W. Coates

  DOI：10.1021/jacs.8b12286

  日期：2019.2.13

  report the regioselective carbonylation of 2,2-disubstituted epoxides to β,β-disubstituted β-lactones. Mechanistic studies revealed epoxide ring-opening as the turnover limiting step, an insight that facilitated the development of improved reaction conditions using weakly donating, ethereal solvents. A wide range of epoxides can be carbonylated to β-lactones, which are subsequently ring-opened to produce

  我们报告了 2,2-二取代环氧化物到 β,β-二取代 β-内酯的区域选择性羰基化。机理研究表明，环氧化物开环是周转限制步骤，这一见解有助于使用弱供体的醚溶剂开发改进的反应条件。广泛的环氧化物可以羰基化为 β-内酯，随后开环产生基于酮的醛醇加合物，为 Mukaiyama 醛醇反应提供替代方案。对映纯的环氧化物被证明经过羰基化/开环过程并保留立体化学以形成对映纯的 β-羟基酯。