4'-deoxyerythromycin A

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4'-deoxyerythromycin A
• 英文别名: (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2S,4S,6S)-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• 化学式: C₃₇H₆₇NO₁₂
• 分子量: 717.938
• InChiKey: MGLILVGTNRMHCT-AFIUOTPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  50
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  4'-deoxyerythromycin A 在 甲醇 、 sodium tetrahydroborate 、 碘 、 sodium acetate 、 二异丙胺 作用下， 以 乙腈 为溶剂， 生成 (3R,4S,5S,6R,7R,9R,10S,11S,12R,13S,14R)-14-ethyl-7,10,12,13-tetrahydroxy-6-((2S,3R,4S,6R)-3-hydroxy-4-(isopropyl(methyl)amino)-6-methyltetrahydro-2H-pyran-2-yloxy)-4-((2S,4S,6S)-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yloxy)-3,5,7,9,11,13-hexamethyloxacyclotetradecan-2-one
  参考文献：
  名称：

  The role of the 4′′-hydroxyl on motilin agonist potency in the 9-dihydroerythromycin series

  摘要：

  The role of the erythromycin 4 ''-hydroxyl group has been explored on the motilin agonist potential in the 9-dihydroerythromycin series of motilides. The compounds show potencies 2- to 4-fold superior to the corresponding hydroxylated compounds. The relationship is maintained when the 9-hydroxyl is alkylated to generate the corresponding 4 ''-deoxy-9-O-acetamido-9-dihydroerythromycins. However, concomitant with this increase in potency is an increase in hERG inhibition. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.078
• 作为产物：
  描述：

  红霉素 在 5-苯基四氮唑 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 36.17h， 生成 4'-deoxyerythromycin A
  参考文献：
  名称：

  基于催化亚磷酰胺转移的羟基位点选择性脱氧方法

  摘要：

  选择性：使用易于合成的亚磷酰胺和四唑催化剂对简单和复杂的天然产物进行脱氧可以作为两步过程进行，无需分离中间脱氧前体。此外，基于肽的四唑催化剂控制脱氧红霉素合成的位点选择性（参见方案），从而克服了未受保护的红霉素 A 的臭名昭著的挑战。

  DOI：

  10.1002/anie.201109033

文献信息

• Synthesis of 4''-Deoxy Motilides: Identification of a Potent and Orally Active Prokinetic Drug Candidate
  作者：Paul A. Lartey、Hugh N. Nellans、Ramin Faghih、Albert Petersen、Carla M. Edwards、Leslie Freiberg、Sherry Quigley、Kennan Marsh、Larry L Klein、Plattner Jacob J.

  DOI：10.1021/jm00010a024

  日期：1995.5

  As an approach to discovering highly potent motilides with oral activity, novel 4''-deoxy derivatives of 8,9-anhydroerythromycin 6,9-hemiacetal were designed, synthesized, and evaluated for their gastrointestinal prokinetic activities. These compounds were orders of magnitude more potent than their 4''-hydroxy analogs in inducing smooth muscle contractions in an in vitro rabbit duodenal assay. Removal of the 12-hydroxy group, which was aimed at improving oral bioavailability, also afforded further potentiation in in vitro activity, leading to the identification of 8,9-anhydro-4''-deoxy-3'-N-desmethyl-3'-N-ethylerythromycin B 6,9-hemiacetal (ABT-229) as a potential prokinetic drug. ABT-229 was >300 000 times more potent than erythromycin in, vitro and had 39% oral bioavailability in dog compared to its 4'';12-dihydroxy congener (EM-523), which was only 400 times more potent than erythromycin and had relatively low (1.4%) oral bioavailability.
• FUDZIVARA, TATSURO;XONDA, EHJITI;XIRANO, TAKAO;SAKAKIBARA, XIDEHO
  作者：FUDZIVARA, TATSURO、XONDA, EHJITI、XIRANO, TAKAO、SAKAKIBARA, XIDEHO

  DOI：——

  日期：——
• Synthesis of 8(R),9(R)-9-deoxo-4''-deoxy-6,9-epoxyerythromycin: potent motilides
  作者：Ramin Faghih、Cynthia Burnell-Curty、Paul A. Lartey、Albert Petersen、Larry L. Klein、Youssef L. Bennani、Hugh N. Nellans

  DOI：10.1016/s0223-5234(99)80059-2

  日期：1999.3

  A series of new and potent motilides, 8(R),9(R)-9-deoxo-4 "-deoxy-6,9-epoxyerythromycin A was designed, synthesized and evaluated for gastrointestinal prokinetic activity. These compounds were acid-stable with many demonstrating in vitro potency markedly superior to erythromycin. (C) Elsevier, Paris.
• US7582611B2
  申请人：——

  公开号：US7582611B2

  公开（公告）日：2009-09-01
• An Approach to the Site-Selective Deoxygenation of Hydroxy Groups Based on Catalytic Phosphoramidite Transfer
  作者：Peter A. Jordan、Scott J. Miller

  DOI：10.1002/anie.201109033

  日期：2012.3.19

  Selective: The deoxygenation of simple and complex natural products employing a readily synthesized phosphoramidite and tetrazole catalysts can be executed as a two‐step process, without the need to isolate intermediate deoxygenation precursors. Furthermore, a peptide‐based tetrazole catalyst controls the site selectivity of deoxyerythromycin synthesis (see scheme), thus overcoming the notorious challenges

  选择性：使用易于合成的亚磷酰胺和四唑催化剂对简单和复杂的天然产物进行脱氧可以作为两步过程进行，无需分离中间脱氧前体。此外，基于肽的四唑催化剂控制脱氧红霉素合成的位点选择性（参见方案），从而克服了未受保护的红霉素 A 的臭名昭著的挑战。