(3aS,7aS)-1,3-bis[(4-bromophenyl)methyl]-2-chlorooctahydro-2-(2-propenyl)-1H-1,3,2-benzodiazasilole | 547713-49-5

• 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: (3aS,7aS)-1,3-bis[(4-bromophenyl)methyl]-2-chlorooctahydro-2-(2-propenyl)-1H-1,3,2-benzodiazasilole
• 英文别名: (S,S)-Leighton reagent；(S,S)-2-allyl-1,3-bis-(4-bromobenzyl)-2-chlorooctahydro-2-1H-1,3,2-benzodiazasilole；(3aS,7aS)-2-Allyl-1,3-bis(4-bromobenzyl)-2-chlorooctahydro-1H-benzo[d][1,3,2]diazasilole；(3aS,7aS)-1,3-bis[(4-bromophenyl)methyl]-2-chloro-2-prop-2-enyl-3a,4,5,6,7,7a-hexahydrobenzo[d][1,3,2]diazasilole
• CAS: 547713-49-5
• 化学式: C₂₃H₂₇Br₂ClN₂Si
• 分子量: 554.827
• InChiKey: JTYONYYNZDUUGN-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-氯-1-己烯 、 (3aS,7aS)-1,3-bis[(4-bromophenyl)methyl]-2-chlorooctahydro-2-(2-propenyl)-1H-1,3,2-benzodiazasilole 在 Hoveyda-Grubbs catalyst second generation 作用下， 以 氯仿 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  A “Methyl Extension” Strategy for Polyketide Natural Product Linker Site Validation and Its Application to Dictyostatin

  摘要：

  An approach to the validation of linker strategies for polyketide natural products with few or no obvious handles for linker attachment, and its application to dictyostatin, are described. Analogues in which the C(6)- and C(12)-methyl groups were replaced by 4-azidobutyl groups were prepared and shown to retain the low nanomolar potency of dictyostatin. Further, conjugation of the C(6) analogue with a cyclooctyne resulted in only minor attenuations in potency. Together, these results shed light on the binding of dictyostatin to beta-tubulin, establish a validated linker strategy for dictyostatin, and set the stage for the synthesis and study of dictyostatin conjugates.

  DOI：

  10.1021/jacs.5b09869
• 作为产物：
  描述：

  (1S,2S)-N,N'-bis-(4-bromo-benzyl)-cyclohexane-1,2-diamine 、 丙烯基三氯硅烷 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以94%的产率得到(3aS,7aS)-1,3-bis[(4-bromophenyl)methyl]-2-chlorooctahydro-2-(2-propenyl)-1H-1,3,2-benzodiazasilole
  参考文献：
  名称：

  角鲨烯合酶抑制剂萨拉戈齐酸 C 的可控低聚自洽合成

  摘要：

  尽管手性天然产物中重复亚基很普遍，但立体控制的低聚化在很大程度上是一种尚未开发的碳骨架构建策略。本报告描述了在受控低聚反应中使用甲硅烷基乙醛酸作为偶极乙醇酸合成子，以有效构建角鲨烯合酶抑制剂 zaragozic 酸 C。这种新方法允许快速、立体控制地形成具有理想保护基团方案的碳骨架，同时最大限度地减少官能团修复和氧化态操作。

  DOI：

  10.1021/ja808347q
• 作为试剂：
  描述：

  methyl 2-((2S,4S,6S)-6-(2-((4-methoxybenzyl)oxy)ethyl)-2-phenyl-1,3-dioxan-4-yl)acetate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 potassium tert-butylate 、 二异丁基氢化铝 、 scandium tris(trifluoromethanesulfonate) 、 (3aS,7aS)-1,3-bis[(4-bromophenyl)methyl]-2-chlorooctahydro-2-(2-propenyl)-1H-1,3,2-benzodiazasilole 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 ethyl 2-((2S,4S,6S)-6-(((2S,4S,6S)-6-(2-((4-methoxybenzyl)oxy)ethyl)-2-phenyl-1,3-dioxan-4-yl)methyl)-2-phenyl-1,3-dioxan-4-yl)acetate
  参考文献：
  名称：

  Cryptocaryols A and B: Total Syntheses, Stereochemical Revision, Structure Elucidation, and Structure–Activity Relationship

  摘要：

  The first total syntheses and structural elucidation of cryptocaryol A and ayptocaryol B were achieved in 23 and 25 linear steps, respectively. The synthesis relied on the use Of a key pseudo-C, symmetric pentaol intermediate, which in a stereochemically divergent manner was converted into either enantiomer as well as diastereomers. This synthetic effort enabled the first structure-activity relationships of this class of PDCD4 stabilizing natural products.

  DOI：

  10.1021/ja404401f

文献信息

• Synthesis and cytotoxic activities of goniothalamins and derivatives
  作者：Anja Weber、Katja Döhl、Julia Sachs、Anja C.M. Nordschild、Dennis Schröder、Andrea Kulik、Thomas Fischer、Lutz Schmitt、Nicole Teusch、Jörg Pietruszka

  DOI：10.1016/j.bmc.2017.02.004

  日期：2017.11

  Antiproliferative activity was measured on three human cancer cell lines (A549, MCF-7, HBL-100), to show which of the structural elements of goniothalamins is mandatory for cytotoxicity. We found that the configuration of the stereogenic centre of the δ-lactone plays an important role for cytotoxicity. In our studies only (R)-configured goniothalamins showed antiproliferative activity, whereby (R)-configuration

  含有环丙烷基团的取代的鸟胆素可以高效地制备，并具有很高的选择性。在三种人类癌细胞系（A549，MCF-7，HBL-100）上测定了抗增殖活性，以显示淋菌素的哪些结构元素对细胞毒性具有强制性。我们发现，δ-内酯的立体中心的构型在细胞毒性中起重要作用。在我们的研究中，只有（R）构型的鞘脂素显示出抗增殖活性，其中（R）构型与天然的Goniothalamin（R）-1一致。另外，δ-内酯需要不饱和，而我们的结果表明乙烯基双键对于细胞毒性不是强制性的。此外，通过双重的体外和体内策略，我们确定了化合物对酵母蛋白Pdr5的抑制作用。
• Total Synthesis of Tetrahydrolipstatin and Stereoisomers via a Highly Regio- and Diastereoselective Carbonylation of Epoxyhomoallylic Alcohols
  作者：Michael Mulzer、Brandon J. Tiegs、Yanping Wang、Geoffrey W. Coates、George A. O’Doherty

  DOI：10.1021/ja505639u

  日期：2014.7.30

  A concise enantioselective synthesis of tetrahydrolipstatin (THL) and seven stereoisomers has been achieved. The synthesis of THL was accomplished in 10 steps and 31% overall yield from an achiral ynone. Key to the success of the approach is the use of a bimetallic [Lewis acid]+[Co(CO)4]− catalyst for a late-stage regioselective carbonylation of an enantiomerically pure cis-epoxide to a trans-β-lactone

  已经实现了四氢脂抑素 (THL) 和七种立体异构体的简明对映选择性合成。THL 的合成分 10 步完成，来自非手性炔酮的总产率为 31%。该方法成功的关键是使用双金属 [路易斯酸]+[Co(CO)4]- 催化剂将对映体纯顺式环氧化物的后期区域选择性羰基化反应为反式-β-内酯。这条通往 THL 及其立体异构体的路线的成功也证明了羰基化催化剂在复杂分子合成中的实用性及其官能团兼容性。
• Formal Total Synthesis of RK-397 via an Asymmetric Hydration and Iterative Allylation Strategy
  作者：Haibing Guo、Matthew S. Mortensen、George A. O’Doherty

  DOI：10.1021/ol801055b

  日期：2008.7.17

  A formal total synthesis of the oxopentaene macrolide antibiotic RK-397 has been achieved. Nine stereocenters were established by a combination of allylation and our asymmetric hydration reactions and a 1,5 anti-selective aldol reaction. The synthesis proceeded in 19 steps from simple achiral conjugated dienoates.

  氧戊烯大环内酯类抗生素RK-397的正式合成已经完成。通过烯丙基化和我们的不对称水合反应和1,5反选择性羟醛反应的组合建立了九个立体中心。由简单的非手性共轭二烯酸酯以19个步骤进行合成。
• Syk 억제제
  申请人：GILEAD SCIENCES, INC. 길리애드 사이언시즈, 인코포레이티드(519990290219)

  公开号：KR20160037198A

  公开（公告）日：2016-04-05

  본 개시내용은 Syk 억제제인 화합물, 및 암 및 염증성 상태를 비롯한 다양한 질환 상태의 치료에서의 그의 용도에 관한 것이다. 특정한 실시양태에서, 화합물의 구조는 하기 화학식 I로 주어진다. 003c#화학식 I003e# 상기 식에서, X, X, X, R, R, R, R, 및 Y는 본원에 기재된 바와 같다. 본 개시내용은 화학식 I의 화합물 또는 그의 제약상 허용되는 염을 포함하는 제약 조성물, 및 Syk에 의해 매개되는 상태를 치료하기 위해 이들 화합물 및 조성물을 사용하는 방법을 추가로 제공한다.

  This text appears to be a scientific or technical document discussing the therapeutic uses of a compound called Syk inhibitor in the treatment of various conditions including cancer and inflammatory diseases. It also mentions the chemical structure of the compound given by the chemical formula I. In the formula, X, X, X, R, R, R, R, and Y are as described in the specification. The document further provides methods for using these compounds and compositions containing compounds or salts thereof of the chemical formula I to treat conditions mediated by Syk.
• Asymmetric Iterative Hydration of Polyene Strategy to Cryptocaryols A and B
  作者：George O’Doherty、Thomas Hunter、Yanping Wang、Jiamin Zheng

  DOI：10.1055/s-0035-1561607

  日期：——

  development of two iterative asymmetric hydration approaches to the synthesis of all syn- and syn/anti/syn-1,3,5,7-tetraol motifs is described. These pseudo-symmetric products are synthetic precursors for 1,3-hexol products. The utility of the route to the all syn-1,3,5,7-tetraol diastereoisomer was demonstrated with its use in the synthesis of cryptocaryols A and B, as well as, stereoisomers. The development

  摘要 两种迭代不对称水合的发展接近所有的合成顺式-和顺式/反/顺式-1,3,5,7四醇基序进行说明。这些伪对称产物是1，3-己醇产物的合成前体。证明了该路线对所有syn -1,3,5,7-四醇非对映异构体的实用性，并证明其可用于合成隐甲酚A和B，以及立体异构体。 两种迭代不对称水合的发展接近所有的合成顺式-和顺式/反/顺式-1,3,5,7四醇基序进行说明。这些伪对称产物是1，3-己醇产物的合成前体。证明了该路线对所有syn -1,3,5,7-四醇非对映异构体的实用性，并证明其可用于合成隐甲酚A和B，以及立体异构体。