(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[[(3aR,4S,6R,7aS)-2-(1-adamantylimino)-1,6-dimethyl-4,6,7,7a-tetrahydro-3aH-pyrano[4,3-d][1,3]oxazol-4-yl]oxy]-2-ethyl-3,4-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecane-7,15-dione

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[[(3aR,4S,6R,7aS)-2-(1-adamantylimino)-1,6-dimethyl-4,6,7,7a-tetrahydro-3aH-pyrano[4,3-d][1,3]oxazol-4-yl]oxy]-2-ethyl-3,4-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecane-7,15-dione
• 化学式: C₂₃H₃₁N₂O₆Pol
• 分子量: 908.2
• InChiKey: RVHCIHJXTYJTIU-WOKNQVIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  64
• 可旋转键数：
  8
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  196
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[[(3aR,4S,6R,7aS)-2-(1-adamantylimino)-1,6-dimethyl-4,6,7,7a-tetrahydro-3aH-pyrano[4,3-d][1,3]oxazol-4-yl]oxy]-2-ethyl-3,4-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecane-7,15-dione 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Regioselective Incorporation of Backbone Constraints Compatible with Traditional Solid-Phase Peptide Synthesis

  摘要：

  A protected aldehyde was attached via a two-carbon spacer to a peptide backbone amide nitrogen during a traditional Merrifield solid-phase synthesis. Acid-mediated unmasking of the aldehyde triggered the regioselective formation of cyclic N-acyliminiums between the aldehyde and the neighboring peptide amide nitrogen. In the absence of an internal nucleophile, the cyclic iminiums formed dihydropyrazinones, a six-membered peptide backbone constraint between two peptide amides. In the presence of an internal nucleophile, tetrahydropyrazinopyrimidinediones or tetrahydroimidazopyrazinediones were formed via tandem N-acyliminium ion cyclization-nucleophilic addition. The outcome of this nucleophilic addition was dependent on the substituent on the nitrogen nucleophile.

  DOI：

  10.1021/co300125m
• 作为产物：
  描述：

  2-[(4S,10aS)-4-methyl-10-(4-nitrophenyl)sulfonyl-3-oxo-8-(trifluoromethyl)-4,10a-dihydro-1H-pyrazino[1,2-a]benzimidazol-2-yl]acetamide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 2-巯基乙醇 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成 (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[[(3aR,4S,6R,7aS)-2-(1-adamantylimino)-1,6-dimethyl-4,6,7,7a-tetrahydro-3aH-pyrano[4,3-d][1,3]oxazol-4-yl]oxy]-2-ethyl-3,4-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecane-7,15-dione
  参考文献：
  名称：

  Polymer-Supported Stereoselective Synthesis of Benzimidazolinopiperazinones

  摘要：

  We describe the efficient synthesis of 4,7,8,10-tetrasubstituted-((( 4S 10aS)-3-oxo -3,4,10,10a-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)alkyl)amides on solid phase via tandem N-acyliminium ion cyclization-nucleophilic addition reactions. The synthesis proceeded with complete stereocontrol of a newly formed stereogenic center provided crude material of high purity and used commercially available building blocks under mild reaction conditions.

  DOI：

  10.1021/jo300836c

文献信息

• Polymer-Supported Stereoselective Synthesis of Benzimidazolinopiperazinones
  作者：Naděžda Cankařová、Viktor Krchňák

  DOI：10.1021/jo300836c

  日期：2012.7.6

  We describe the efficient synthesis of 4,7,8,10-tetrasubstituted-((( 4S 10aS)-3-oxo -3,4,10,10a-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)alkyl)amides on solid phase via tandem N-acyliminium ion cyclization-nucleophilic addition reactions. The synthesis proceeded with complete stereocontrol of a newly formed stereogenic center provided crude material of high purity and used commercially available building blocks under mild reaction conditions.
• <i>N</i>′-Substituted-2′-<i>O</i>,3′-<i>N</i>-carbonimidoyl Bridged Macrolides: Novel Anti-inflammatory Macrolides without Antimicrobial Activity
  作者：Martina Bosnar、Goran Kragol、Sanja Koštrun、Ines Vujasinović、Berislav Bošnjak、Vlatka Bencetić Mihaljević、Zorica Marušić Ištuk、Samra Kapić、Boška Hrvačić、Karmen Brajša、Branka Tavčar、Dubravko Jelić、Ines Glojnarić、Donatella Verbanac、Ognjen Čulić、Jasna Padovan、Sulejman Alihodžić、Vesna Eraković Haber、Radan Spaventi

  DOI：10.1021/jm300356u

  日期：2012.7.12

  Macrolide antibiotics, like erythromycin, clarithromycin, and azithromycin, possess anti-inflammatory properties. These properties are considered fundamental to the efficacy of these three macrolides in the treatment of chronic inflammatory diseases like diffuse panbronchiolitis and cystic fibrosis. However, long-term treatment with macrolide antibiotics presents a considerable risk for promotion of bacterial resistance. We have examined antibacterial and anti-inflammatory effects of a novel macrolide class: N'-substituted 2'-O,3'-N-carbonimidoyl bridged erythromycin-derived 14- and 15-membered macrolides. A small focused library was prepared, and compounds without antimicrobial activity, which inhibited IL-6 production, were selected. Data analysis led to a statistical model that could be used for the design of novel anti-inflammatory macrolides. The most promising compound from this library retained the anti-inflammatory activity observed with azithromycin in lipopolysaccharide-induced pulmonary neutrophilia in vivo. Importantly, this study strongly suggests that antimicrobial and anti-inflammatory activities of macrolides are independent and can be separated, which raises development plausibility of novel anti-inflammatory therapeutics.
• Polymer-Supported Stereoselective Synthesis of Tetrahydrobenzopyrazino-thiadiazinone Dioxides via <i>N</i>-Sulfonyl Iminiums
  作者：Naděžda Cankařová、Agustina La Venia、Viktor Krchňák

  DOI：10.1021/co5000163

  日期：2014.6.9

  The stereoselective synthesis of 1,2,11,11a-tetrahydrobenzo [e]pyrazino [1,2-b] [1,2,4] thiadiazin-3 (4H)-one 6,6-dioxides on a solid support via tandem N-sulfonyl iminium ion cydization, followed by nucleophilic addition is reported. The synthesis proceeded with full control of stereoselectivity at the newly formed asymmetric carbon, under mild conditions, and using commercially available building blocks. The synthetic route provided high-purity crude products.
• Regioselective Incorporation of Backbone Constraints Compatible with Traditional Solid-Phase Peptide Synthesis
  作者：Agustina La Venia、Barbora Lemrová、Viktor Krchňák

  DOI：10.1021/co300125m

  日期：2013.1.14

  A protected aldehyde was attached via a two-carbon spacer to a peptide backbone amide nitrogen during a traditional Merrifield solid-phase synthesis. Acid-mediated unmasking of the aldehyde triggered the regioselective formation of cyclic N-acyliminiums between the aldehyde and the neighboring peptide amide nitrogen. In the absence of an internal nucleophile, the cyclic iminiums formed dihydropyrazinones, a six-membered peptide backbone constraint between two peptide amides. In the presence of an internal nucleophile, tetrahydropyrazinopyrimidinediones or tetrahydroimidazopyrazinediones were formed via tandem N-acyliminium ion cyclization-nucleophilic addition. The outcome of this nucleophilic addition was dependent on the substituent on the nitrogen nucleophile.