6,11-Di-O-methylerythromycin A | 81103-14-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6,11-Di-O-methylerythromycin A
• 英文别名: 6-O,11-O-Dimethylerythromycin；(3R,4S,5S,6R,7R,9R,11R,12R,13R,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-13-hydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-7,12-dimethoxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• CAS: 81103-14-2
• 化学式: C₃₉H₇₁NO₁₃
• 分子量: 761.992
• InChiKey: DWRKNXHSSDFLOJ-XNLUWZQGSA-N

物化性质

• 熔点：
  252-257 °C(Solv: dichloromethane (75-09-2); ethyl ether (60-29-7))
• 沸点：
  808.6±65.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、DMSO（微溶、加热）、甲醇（微溶、加热)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  53
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  172
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  6,11-Di-O-methylerythromycin A 在 盐酸 、 水 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.0h， 以78%的产率得到3-O-descladinosyl-6,11-di-O-methylerythromycin A
  参考文献：
  名称：

  Synthesis and antibacterial activity of 3-O-carbamoyl derivatives of 6,11-di-O-methylerythromycin A: A novel class of acylides

  摘要：

  A novel series of acylides, 3-O-carbamoyl derivatives of 6,11-di-O-methylerythromycin A, were synthesized and evaluated for their antibacterial activity. These compounds have significant antibacterial activity against Gram-positive pathogens, including erythromycin-resistant but methicillin-susceptible Staphylococcus aureus, erythromycin-resistant and methicillin-resistant S. aureus, erythromycin-resistant Streptococcus pneumoniae, and Gram-negative pathogens, such as Haemophilus influenzae. Among the derivatives tested, compounds 4p, 4r, 4w, 4x and 4z were found to have potent activity against most susceptible and resistant bacteria. Compound 4p exhibited excellent antibacterial activity in comparison to the others. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.009
• 作为产物：
  描述：

  benzyl [(2S,3R,4S,6R)-6-methyl-4-[methyl(phenylmethoxycarbonyl)amino]-2-[[(3R,4S,5S,6R,7R,9R,11R,12R,13R)-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yl]oxy]oxan-3-yl] carbonate 、 碘甲烷 以85%的产率得到
  参考文献：
  名称：

  MORIMOTO, SHIGEO;MISAWA, YOKO;ADACHI, TAKASHI;NAGATE, TAKATOSHI;WATANABE,+, J. ANTIBIOTICS, 43,(1990) N, C. 286-294

  摘要：

  DOI：

文献信息

• Studies on selectivity of O-methylation of erythromycin derivatives based on molecular mechanics and molecular orbital methods.
  作者：Yutaka KAWASHIMA、Shigeo MORIMOTO、Tohru MATSUNAGA、Masato KASHIMURA、Takashi ADACHI、Yoshiaki WATANABE、Katsuo HATAYAMA、Shuichi HIRONO、Ikuo MORIGUCHI

  DOI：10.1248/cpb.38.1485

  日期：——

  The regioselectivity of O-methylation of the C6- and C11-hydroxyl groups of 2', 4"-O-bis(trimethylsilyl)erythromycin A (3, TMS-EM-A) and that in the case of 2', 4"-O-bis(trimethylsilyl)erythromycin B (4, TMS-EM-B) were examined in relation to the ease of deprotonation and the stability of the anion state. O-Metylation of 3 gave 11-methoxy-TMS-EM-A (5) and 6-methoxy-TMS-EM-A (6) in the ratio of ca.3 : 1, whereas that of 4 gave predominantly 6-methoxy-TMS-EM-B (7). To understand how the steric and electronic structures of EM-A (1) and EM-B (2) affect the selectivities, we carried out theoretical calculations using a semi-empirical molecular orbital method, MNDO. From the frontier electronic density of the lowest unoccupied molecular orbital (LUMO), it was suggested that the activities of deprotonation at the C11-hydroxyl groups of 3 and 4 are higher than those of the C6-hydroxyl groups. On the other hand, it was shown from the total energies of the molecules that the C6-O- -derivatives (3a and 4a) of 3 and 4 are more stable than the C11-O- -derivatives (3b and 4b). The difference of total energies between 4a and 4b is greater than that of 3a and 3b by 5.1kcal/mol, suggesting the possibility of hydrogen bonding between C11-O- and C12-OH of 3b.

  对2', 4"-O-双(trimethylsilyl)红霉素A (3, TMS-EM-A)和2', 4"-O-双(trimethylsilyl)红霉素B (4, TMS-EM-B)的C6和C11羟基的O-甲基化的区域选择性进行了研究，考虑了去质子化的难易程度和阴离子态的稳定性。3的O-甲基化产生了11-甲氧基-TMS-EM-A (5)和6-甲氧基-TMS-EM-A (6)，比例约为3:1，而4的O-甲基化主要产生6-甲氧基-TMS-EM-B (7)。为了了解EM-A (1)和EM-B (2)的立体和电子结构如何影响选择性，我们使用半经验分子轨道方法MNDO进行了理论计算。从最低未占据分子轨道（LUMO）的前沿电子密度来看，表明3和4的C11羟基的去质子化活性高于C6羟基。此外，从分子的总能量可以看出，3和4的C6-O-衍生物（3a和4a）比C11-O-衍生物（3b和4b）更稳定。4a和4b之间的总能量差大于3a和3b之间的差异，差值为5.1 kcal/mol，暗示了3b的C11-O-和C12-OH之间存在氢键的可能性。
• MORIMOTO, SHIGEO;MISAWA, YOKO;ADACHI, TAKASHI;NAGATE, TAKATOSHI;WATANABE,+, J. ANTIBIOTICS, 43,(1990) N, C. 286-294
  作者：MORIMOTO, SHIGEO、MISAWA, YOKO、ADACHI, TAKASHI、NAGATE, TAKATOSHI、WATANABE,+

  DOI：——

  日期：——
• KAWASHIMA, YUTAKA;MORIMOTO, SHIGEO;MATSUNAGA, TOHRU;KASHIMURA, MASATO;ADA+, CHEM. AND PHARM. BULL., 38,(1990) N, C. 1485-1489
  作者：KAWASHIMA, YUTAKA、MORIMOTO, SHIGEO、MATSUNAGA, TOHRU、KASHIMURA, MASATO、ADA+

  DOI：——

  日期：——
• Synthesis and antibacterial activity of 3-O-carbamoyl derivatives of 6,11-di-O-methylerythromycin A: A novel class of acylides
  作者：Zhongyuan Wu、Yong Lu、Ming Luo、Xianran He、Yuling Xiao、Jin Yang、Yuanhu Pan、Guofu Qiu、Hao Guo、Hao Hu

  DOI：10.1016/j.ejmech.2010.05.009

  日期：2010.9

  A novel series of acylides, 3-O-carbamoyl derivatives of 6,11-di-O-methylerythromycin A, were synthesized and evaluated for their antibacterial activity. These compounds have significant antibacterial activity against Gram-positive pathogens, including erythromycin-resistant but methicillin-susceptible Staphylococcus aureus, erythromycin-resistant and methicillin-resistant S. aureus, erythromycin-resistant Streptococcus pneumoniae, and Gram-negative pathogens, such as Haemophilus influenzae. Among the derivatives tested, compounds 4p, 4r, 4w, 4x and 4z were found to have potent activity against most susceptible and resistant bacteria. Compound 4p exhibited excellent antibacterial activity in comparison to the others. (C) 2010 Elsevier Masson SAS. All rights reserved.