14-hydroxy-21-nitro-3β-(α-L-rhamnopyranosyloxy)-5β,14β-pregnane | 145345-81-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 14-hydroxy-21-nitro-3β-(α-L-rhamnopyranosyloxy)-5β,14β-pregnane
• 英文别名: (2R,3R,4R,5R,6S)-2-[[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-nitroethyl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl]oxy]-6-methyloxane-3,4,5-triol
• CAS: 145345-81-9
• 化学式: C₂₇H₄₅NO₈
• 分子量: 511.656
• InChiKey: QRGJTLPIYAQSBZ-DHWVLYFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  14-hydroxy-21-nitro-3β-(α-L-rhamnopyranosyloxy)-5β,14β-pregnane 在 platinum(IV) oxide 氢气 、 溶剂黄146 作用下， 反应 16.0h， 以95%的产率得到21-amino-3β-(α-L-rhamnopyranosyloxy)-5β-pregnan-14β-ol
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 17β-Substituted 14β-Hydroxysteroid 3-(α-l-Rhamnopyranoside)s:  Steroids That Bind to the Digitalis Receptor

  摘要：

  The preparation of 17 beta-substituted 14 beta-hydroxysteroid C-3 alpha-L-rhamnopyranosides is described. These derivatives have a 14 beta,20-ether, 14 beta,20-lactone, or 17 beta-CH2CH2OH, -CH2CH2NH2, -CH=CHNO2(E), -CH=CHCOOH(E), -CH(OH)CH2NO2(R), -CH(OMe)CH2NO2(R), -CH2CH2COOH, or -CH(OH)CH2NH2(R) group. Derivatives were assayed in a radioligand binding assay for [H-3]ouabain in membranes from canine heart muscle. The digitalis ''receptor'' comprises isoenzymes of the ion-pumping enzyme, Na+,K+-ATPase. The 17 beta-CH=CHNO2(E), 17 beta-CH=CHCOOH(E), and 17 beta-CH(OMe)CH2NO2(R) derivatives were the most potent and equivalent to ouabain with low-nanomolar IC50 values. The very potent binding affinity of the disubstituted compound 17 beta-CH(OMe)CH2NO2(R) further demonstrates that 17 beta-unsaturated substitution is not required for potent binding affinity. This observation may be of value in the separation of cardiotonic and cardiotoxic effects. Tosylation of the 17 beta-CH2OH, prepared from the 17 beta-CHO by lithium aluminum hydride reduction, yielded the 14 beta,17 beta-ether. Synthesis of the 17 beta-CH2COOH gave the epimeric 14 alpha,17 alpha- and 14 beta, 17 beta-lactones. Structures have been established by NMR analysis.

  DOI：

  10.1021/jm960880l
• 作为产物：
  描述：

  evomonoside α-L-rhamnopyranoside tribenzoate 在 4-二甲氨基吡啶 、 potassium fluoride 、 ammonium hydroxide 、 sodium tetrahydroborate 、 sodium periodate 、 lithium tri(t-butoxy)aluminum hydride 、 potassium hydrogencarbonate 、 臭氧 、 锌 作用下， 以 甲醇 、 乙醚 、 乙醇 、 异丙醇 为溶剂， 反应 62.0h， 生成 14-hydroxy-21-nitro-3β-(α-L-rhamnopyranosyloxy)-5β,14β-pregnane
  参考文献：
  名称：

  20-羟基-，20-氨基-和20-硝基-14-羟基-21-nor-5 beta，14 beta-孕烷C-3苷和相关衍生物的合成：结合到孕烷上的孕烷的构效关系洋地黄受体。

  摘要：

  描述了14-羟基-21-nor-5β，14β-孕烷和5β，14β-孕烷C-3α-L-鼠李糖苷和tris-β-D-指氧苷的衍生物的制备。这些具有C-17 beta COCH2OH，CH2OH，CO2H，CO2Me，CH2NH2或CH2NO2基团的衍生物可通过放射配体结合测定法与心肌的洋地黄受体识别位点结合。21-去甲链烷衍生物始终显示出比相应的20-α-和20-β-孕烷类似物更高的结合亲和力。C-20硝基鼠李糖苷的结合亲和力与洋地黄毒相当。在迄今为止发现的结合测定中，17β-CH2NO2基团是不饱和内酯的最有效替代物，显示出与强心苷相当的结合亲和力。

  DOI：

  10.1021/jm00053a006

文献信息

• Synthesis of 20-hydroxy-, 20-amino-, and 20-nitro-14-hydroxy-21-nor-5.beta.,14.beta.-pregnane C-3 glycosides and related derivatives: structure-activity relationships of pregnanes that bind to the digitalis receptor
  作者：John F. Templeton、Yangzhi Ling、Talal H. Zeglam、Frank S. LaBella

  DOI：10.1021/jm00053a006

  日期：1993.1

  preparation of derivatives of 14-hydroxy-21-nor-5 beta,14 beta-pregnane and 5 beta,14 beta-pregnane C-3 alpha-L-rhamnosides and tris-beta-D-digitoxosides is described. These derivatives, possessing a C-17 beta COCH2OH, CH2OH, CO2H, CO2Me, CH2NH2, or CH2NO2 group, bind to the digitalis receptor recognition site of heart muscle as measured in a radioligand binding assay. The 21-norpregnane derivatives consistently

  描述了14-羟基-21-nor-5β，14β-孕烷和5β，14β-孕烷C-3α-L-鼠李糖苷和tris-β-D-指氧苷的衍生物的制备。这些具有C-17 beta COCH2OH，CH2OH，CO2H，CO2Me，CH2NH2或CH2NO2基团的衍生物可通过放射配体结合测定法与心肌的洋地黄受体识别位点结合。21-去甲链烷衍生物始终显示出比相应的20-α-和20-β-孕烷类似物更高的结合亲和力。C-20硝基鼠李糖苷的结合亲和力与洋地黄毒相当。在迄今为止发现的结合测定中，17β-CH2NO2基团是不饱和内酯的最有效替代物，显示出与强心苷相当的结合亲和力。
• Synthesis and Structure−Activity Relationships of 17β-Substituted 14β-Hydroxysteroid 3-(α-<scp>l</scp>-Rhamnopyranoside)s:  Steroids That Bind to the Digitalis Receptor
  作者：John F. Templeton、Yangzhi Ling、Kirk Marat、Frank S. LaBella

  DOI：10.1021/jm960880l

  日期：1997.5.1

  The preparation of 17 beta-substituted 14 beta-hydroxysteroid C-3 alpha-L-rhamnopyranosides is described. These derivatives have a 14 beta,20-ether, 14 beta,20-lactone, or 17 beta-CH2CH2OH, -CH2CH2NH2, -CH=CHNO2(E), -CH=CHCOOH(E), -CH(OH)CH2NO2(R), -CH(OMe)CH2NO2(R), -CH2CH2COOH, or -CH(OH)CH2NH2(R) group. Derivatives were assayed in a radioligand binding assay for [H-3]ouabain in membranes from canine heart muscle. The digitalis ''receptor'' comprises isoenzymes of the ion-pumping enzyme, Na+,K+-ATPase. The 17 beta-CH=CHNO2(E), 17 beta-CH=CHCOOH(E), and 17 beta-CH(OMe)CH2NO2(R) derivatives were the most potent and equivalent to ouabain with low-nanomolar IC50 values. The very potent binding affinity of the disubstituted compound 17 beta-CH(OMe)CH2NO2(R) further demonstrates that 17 beta-unsaturated substitution is not required for potent binding affinity. This observation may be of value in the separation of cardiotonic and cardiotoxic effects. Tosylation of the 17 beta-CH2OH, prepared from the 17 beta-CHO by lithium aluminum hydride reduction, yielded the 14 beta,17 beta-ether. Synthesis of the 17 beta-CH2COOH gave the epimeric 14 alpha,17 alpha- and 14 beta, 17 beta-lactones. Structures have been established by NMR analysis.