(1R,4S,5R,6S)-5,6-bis((tert-butyldimethylsilyl)oxy)-2-azabicyclo[2.2.1]heptan-3-one | 872174-25-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1R,4S,5R,6S)-5,6-bis((tert-butyldimethylsilyl)oxy)-2-azabicyclo[2.2.1]heptan-3-one
• 英文别名: (1R,4S,5R,6S)-5,6-bis[[tert-butyl(dimethyl)silyl]oxy]-2-azabicyclo[2.2.1]heptan-3-one
• CAS: 872174-25-9
• 化学式: C₁₈H₃₇NO₃Si₂
• 分子量: 371.668
• InChiKey: DWKRFVWYXLJZRI-YJNKXOJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,4S,5R,6S)-5,6-bis((tert-butyldimethylsilyl)oxy)-2-azabicyclo[2.2.1]heptan-3-one 在 盐酸 作用下， 生成 (1S,2R,3S,4R)-4-Amino-2,3-dihydroxy-cyclopentanecarboxylic acid; hydrochloride
  参考文献：
  名称：

  将氨基环戊烷羧酸接枝到RGD三肽序列上会产生低纳摩尔浓度的alphaVbeta3 / alphaVbeta5整联蛋白双结合剂。

  摘要：

  以手性非外消旋形式制备了11个γ-氨基环戊烷羧酸（Acpca）平台，包括四个二羟基代表分子（19-22），三个羟基类似物（34-36）和四个脱氧衍生物（30-33）。然后通过混合固相/溶液方案将这些简单的单元嫁接到Arg-Gly-Asp（RGD）三肽构架上，从而提供11种环-[-Arg-Gly-Asp-Acpca-]型大环类似物的集合体-11。评价各个化合物对αVbeta3和αVbeta5整联蛋白受体的结合亲和力。与参考化合物EMD121974和ST1646相比，类似物10表现出非常有趣的活性谱（IC50 / alphaVbeta3 = 1.5 nM； IC50 / alphaVbeta5 = 0.59 nM）。密切相关的同类物6、8 和9也被证明是出色的双重粘合剂，其活性水平在低纳摩尔范围内。确定了三维（3D）NMR溶液结构，并在选定的类似物上与参照化合物EMD121974进行了整合素α

  DOI：

  10.1021/jm050698x
• 作为产物：
  描述：

  (1'S,2'R,5R)-1-benzyl-5-[1-(tert-butyldimethylsilanyloxy)-2,3-dihydroxypropyl]pyrrolidin-2-one 在 sodium periodate 、 sodium 、 silica gel 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 氨 、 水 为溶剂， 反应 2.5h， 生成 (1R,4S,5R,6S)-5,6-bis((tert-butyldimethylsilyl)oxy)-2-azabicyclo[2.2.1]heptan-3-one
  参考文献：
  名称：

  Variable Strategy toward Carbasugars and Relatives. 4.¹ Viable Access to (4a-Carbapentofuranosyl)amines, (5a-Carbahexopyranosyl)amines, and Amino Acids Thereof

  摘要：

  A chiral, divergent synthesis of two carbafuranosylamines, I and 2, two carbapyranosylamines, 3 and 4, two carbafuranosylamino acids, 5 and 6, and two carbapyranosylamino acids, 7 and 8, has been achieved. Highlights of the procedure include the following: a diastereoselective crossed vinylogous Mukaiyama aldol coupling between N-(tert-butoxycarbonyl)-2-[(tert-butyldimethylsilyl)oxy]pyrrole (TBSOP, 9) and 2,3-O-isopropylidene-D-glyceraldehyde (10) for the assembly of the target compound carbon backbone; a high-yielding silylative cycloaldolization that gives the cyclopentanoid and cyclohexanoid motifs; and a reductive or hydrolytic breakage of the lactam C(O)-N link to liberate the carbasugar and install the desired pseudo-anomeric amine and the hydroxymethyl or carboxyl functionalities. The sequences leading to trans-configured carbafuranosyl compounds 1 and 5 and carbapyranosyl compounds 3 and 7 were 12- and 13-step processes, with overall yields of 34%, 35%, 17%, and 16%. Cis-configured isomers 2, 4, 6, and 8 were obtained only in minor yields.

  DOI：

  10.1021/jo0257905

文献信息

• [EN] 2'3'-CYCLIC DINUCLEOTIDE ANALOGUE COMPRISING A CYCLOPENTANYL MODIFIED NUCLEOTIDE<br/>[FR] ANALOGUE DE DINUCLÉOTIDE 2'3'-CYCLIQUE COMPRENANT UN NUCLÉOTIDE MODIFIÉ PAR CYCLOPENTANYLE
  申请人：INST OF ORGANIC CHEMISTRY AND BIOCHEMISTRY ASCR V V I

  公开号：WO2019211799A1

  公开（公告）日：2019-11-07

  The present disclosure relates to 2'3'-cyclic dinucleotides comprising a carbocyclic nucleotide and derivatives thereof, that can modulate the activity of the STING adaptor protein.

  本公开涉及包括碳环核苷酸及其衍生物的2'3'-环二核苷酸，可以调节STING适配蛋白的活性。
• 2'3' CYCLIC DINUCLEOTIDES WITH PHOSPHONATE BOND ACTIVATING THE STING ADAPTOR PROTEIN
  申请人：INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY ASCR,V.V.I.

  公开号：US20190185510A1

  公开（公告）日：2019-06-20

  The present disclosure relates to 2′3′ cyclic phosphonate dinucleotides of general formula (J), their pharmaceutically acceptable salts, their pharmaceutical composition and combinations of said substances and other medicaments or pharmaceuticals. The disclosure also relates to the use of said compounds for the treatment or prevention of diseases or conditions modifiable by STING protein modulation, such as cancer or viral, allergic and inflammatory diseases. In addition, these substances can be used as adjuvants in vaccines.

  本公开涉及一般式（J）的2′3′环磷酸二核苷酸，其药用可接受盐，其药物组合物以及所述物质与其他药物或药品的组合物。该公开还涉及使用所述化合物治疗或预防可通过STING蛋白调节改变的疾病或状况，如癌症或病毒性、过敏性和炎症性疾病。此外，这些物质可用作疫苗的辅助剂。
• [EN] 3'3'-CYCLIC DINUCLEOTIDE ANALOGUE COMPRISING A CYCLOPENTANYL MODIFIED NUCLEOTIDE AS STING MODULATOR<br/>[FR] ANALOGUE DU DINUCLÉOTIDE 3'3'-CYCLIQUE COMPRENANT UN NUCLÉOTIDE MODIFIÉ PAR CYCLOPENTANYLE UTILISÉ EN TANT QUE MODULATEUR DE STING
  申请人：INST OF ORGANIC CHEMISTRY AND BIOCHEMISTRY ASCR V V I

  公开号：WO2020178768A1

  公开（公告）日：2020-09-10

  The present disclosure relates to 3'3'-cyclic dinucleotides comprising a carbocyclic nucleotide and derivatives thereof, that can modulate the activity of the STING adaptor protein.

  本公开涉及包含碳环核苷酸及其衍生物的3'3'-环二核苷酸，可以调节STING适配蛋白的活性。