Erythromycin, 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-I+/--L-ribo-hexopyranosyl)oxy]-11,12-dideoxy-11,12-(hydrazonocarbonyloxy)-6-O-methyl-3-oxo- | 172822-30-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Erythromycin, 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-I+/--L-ribo-hexopyranosyl)oxy]-11,12-dideoxy-11,12-(hydrazonocarbonyloxy)-6-O-methyl-3-oxo-
• 英文别名: (1S,2R,5R,7R,8R,9R,11R,13R,14R)-15-amino-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone
• CAS: 172822-30-9
• 化学式: C₃₁H₅₃N₃O₁₀
• 分子量: 627.776
• InChiKey: UPJBSBKTMAQGDK-UABILYANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  44
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  167
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  Erythromycin, 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-I+/--L-ribo-hexopyranosyl)oxy]-11,12-dideoxy-11,12-(hydrazonocarbonyloxy)-6-O-methyl-3-oxo- 在 palladium on activated charcoal 盐酸 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0 ℃ 、151.99 kPa 条件下， 反应 195.0h， 生成
  参考文献：
  名称：

  Synthesis of 9-oxime-11,12-carbamate ketolides Through a novel N-deamination reaction of 11,12-hydrazonocarbamate ketolide

  摘要：

  A series of 9-oxime-11,12-carbamate ketolides was synthesized for the first time through a key 11,12-hydrazonocarbamate intermediate that was first oximated and further deaminated to give the corresponding carbamate. The N-N bond cleavage was achieved through an original new reaction using glycoaldehyde dimer as deaminating reagent. The new compounds synthesized were shown to display improved antibacterial activities against Streptococcus pneumoniae and S. pyogenes resistant to erythromycin. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00147-0
• 作为产物：
  描述：

  克拉霉素 在 吡啶 、 盐酸 、 三氟乙酸吡啶 、 sodium hydride 、 potassium carbonate 、 一水合肼 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 水 、 丙酮 、 乙腈 为溶剂， 反应 55.0h， 生成 Erythromycin, 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-I+/--L-ribo-hexopyranosyl)oxy]-11,12-dideoxy-11,12-(hydrazonocarbonyloxy)-6-O-methyl-3-oxo-
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens

  摘要：

  In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11,12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLS(B) resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.

  DOI：

  10.1021/jm980240d

文献信息

• 3-Keto-11,12-carbazate Derivatives of 6-0-Methylerythromycin A Synthesis and In Vitro Activity.
  作者：GEORGE GRIESGRABER、YAT SUN OR、DANIEL T. W. CHU、ANGELA M. NILIUS、PAULINE M. JOHNSON、ROBERT K. FLAMM、RODGER F. HENRY、JACOB J. PLATTNER

  DOI：10.7164/antibiotics.49.465

  日期：——

  The 11, 12-cyclic carbazate of 3-keto-6-O-methylerythromycin A (4) was prepared. This compound shows in vitro antibacterial activity comparable to erythromycin A (1) against erythromycin-susceptible organisms and increased activity against some erythromycin-resistant organisms. Using 4 as a lead, a series of analogues was prepared by acylation or alkylation of the carbazate nitrogen. Several of the N-alkylated derivatives showed dramatically improved antibacterial activity against both susceptible and resistant organisms as compared to erythromycin A.

  制备出了 3-酮-6-O-甲基红霉素 A 的 11，12-环咔嗪酸盐（4）。该化合物对红霉素易感菌的体外抗菌活性与红霉素 A（1）相当，对某些红霉素耐药菌的活性也有所提高。以 4 为先导，通过对肼基氮进行酰化或烷基化，制备了一系列类似物。与红霉素 A 相比，几种 N-烷基化衍生物对易感和耐药生物的抗菌活性都有显著提高。
• Synthesis and Antibacterial Activity of Ketolides (6-<i>O</i>-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens
  作者：Constantin Agouridas、Alexis Denis、Jean-Michel Auger、Yannick Benedetti、Alain Bonnefoy、François Bretin、Jean-François Chantot、Arlette Dussarat、Claude Fromentin、Solange Gouin D'Ambrières、Sylvette Lachaud、Patrick Laurin、Odile Le Martret、Véronique Loyau、Nicole Tessot

  DOI：10.1021/jm980240d

  日期：1998.10.1

  In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11,12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLS(B) resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.
• Synthesis of 9-oxime-11,12-carbamate ketolides Through a novel N-deamination reaction of 11,12-hydrazonocarbamate ketolide
  作者：Alexis Denis、Jean-Marie Pejac、François Bretin、Alain Bonnefoy

  DOI：10.1016/s0968-0896(03)00147-0

  日期：2003.5.29

  A series of 9-oxime-11,12-carbamate ketolides was synthesized for the first time through a key 11,12-hydrazonocarbamate intermediate that was first oximated and further deaminated to give the corresponding carbamate. The N-N bond cleavage was achieved through an original new reaction using glycoaldehyde dimer as deaminating reagent. The new compounds synthesized were shown to display improved antibacterial activities against Streptococcus pneumoniae and S. pyogenes resistant to erythromycin. (C) 2003 Elsevier Science Ltd. All rights reserved.