甲醇(6 -乙酰吗啡) | 2784-73-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 中文名称: 甲醇(6 -乙酰吗啡)
• 中文别名: 甲醇(6-乙酰吗啡)
• 英文名称: 6-monoacetylmorphine
• 英文别名: 6-acetylmorphine；6-MAM；6-O-acetylmorphine；6-AM；[(4R,4aR,7S,7aR,12bS)-9-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl] acetate
• CAS: 2784-73-8；29593-26-8
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: JJGYGPZNTOPXGV-SSTWWWIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  库房应保持通风、低温和干燥。

反应信息

• 作为反应物：
  描述：

  甲醇(6 -乙酰吗啡) 在 sodium hydroxide 作用下， 生成 吗啡
  参考文献：
  名称：

  Circular dichroism spectra of opium alkaloids in aqueous media

  摘要：

  DOI：

  10.1021/ac00224a007
• 作为产物：
  描述：

  吗啡 在 盐酸羟胺 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 17.0h， 生成 甲醇(6 -乙酰吗啡)
  参考文献：
  名称：

  一种吗啡衍生物的合成方法及应用

  摘要：

  本发明公开了一种吗啡衍生物的合成方法，该方法以吗啡为起始原料，经选择性保护和糖基化，从而得到目的产物；本发明合成方法得到的M3G，其HPLC的纯度可以达到99.8％，可以作为相关产品质量研究时的对照品或标准品使用。

  公开号：

  CN107964030B

文献信息

• Diamorphine stability in aqueous solution for subcutaneous infusion
  作者：O A Omar、P J Hoskin、A Johnston、G W Hanks、P Turner

  DOI：10.1111/j.2042-7158.1989.tb06452.x

  日期：2011.4.12

  The influence of temperature and concentration on diamorphine stability during storage over 8 weeks has been investigated. Ampoules containing diamorphine hydrochloride in concentrations from 0·98–250 mg mL−1 have been stored at −20, 4, 21 and 37°C for 8 weeks. Their content of diamorphine, 6-monoacetylmorphine and morphine, on measurement by high performance liquid chromatography after 1, 2, 4, 6 and 8 weeks storage changed to slow degradation of diamorphine at all concentrations at temperatures of 4°C and above. This was accompanied by a corresponding increase in 6-monoacetylmorphine and morphine. There was an associated fall in pH and development of a strong odour characteristic of acetic acid. Precipitation and a white turbidity seen in solutions of 15·6 mg mL and above, appeared after 2 weeks incubation.

  温度和浓度对地西泮在8周存储期间稳定性的影响已经被调查。含有地西泮盐酸盐，浓度从0.98-250毫克/毫升的安瓿在-20、4、21和37摄氏度下存储了8周。经过1、2、4、6和8周存储后，通过高效液相色谱测量，地西泮、6-单乙酰吗啡和吗啡的含量在4摄氏度及以上的所有浓度下发生缓慢降解。这伴随着6-单乙酰吗啡和吗啡的相应增加。伴随着pH值下降和产生乙酸特征性的强烈气味。在15.6毫克/毫升及以上的溶液中出现的沉淀和白色浑浊物，在孵育2周后出现。
• The effect of temperature and pH on the deacetylation of diamorphine in aqueous solution and in human plasma
  作者：David A Barrett、Astrid L P Dyssegaard、P Nicholas Shaw

  DOI：10.1111/j.2042-7158.1992.tb05474.x

  日期：2011.4.12

  The effect of temperature on the kinetics of the deacetylation of diamorphine and 6-monoacetylmorphine was studied in human plasma. Diamorphine was rapidly and quantitatively degraded to 6-monoacetylmorphine with initial half-lives of 354, 18 and 3 min at temperatures of 4, 25 and 37°C, respectively. Further deacetylation to morphine was not detected. In aqueous solution, diamorphine was quantitatively degraded to give 6-monoacetylmorphine as the major product and morphine as a minor product, the rate of deacetylation being dependent on temperature and pH. At pH 4·0 and 5·6 diamorphine had a half-life of greater than 14 days at all temperatures but at alkaline pH diamorphine was rapidly deacetylated. The rate of deacetylation of 6-monoacetylmorphine was consistently slower than that of diamorphine under identical conditions of pH and temperature. A method is described for the rapid stabilization and subsequent assay of diamorphine in plasma which will prevent errors in estimation of the drug due to unwanted hydrolysis.

  温度对吗啡和6-单乙酰吗啡去乙酰化动力学的影响在人类血浆中进行了研究。吗啡在4、25和37°C下的初始半衰期分别为354、18和3分钟，迅速且定量地降解为6-单乙酰吗啡。进一步的去乙酰化生成吗啡未被检测到。在水溶液中，吗啡被定量降解，主要生成6-单乙酰吗啡和少量吗啡，去乙酰化速率取决于温度和pH值。在pH 4.0和5.6下，吗啡在所有温度下的半衰期均大于14天，但在碱性pH下，吗啡会迅速去乙酰化。在相同的pH和温度条件下，6-单乙酰吗啡的去乙酰化速率始终比吗啡慢。描述了一种快速稳定和随后在血浆中测定吗啡的方法，可防止由于不必要的水解而导致对药物估计的错误。
• Synthesis and characterization of novel color chemosensors based on azo dyes for possible application in opioid pharmacology
  作者：Afaf R. Genady

  DOI：10.1002/jhet.436

  日期：——

  give morphine azo dyes. The coupling of the diazotized 4,4′-diaminostilbene with M or 6-AM in ratio 1:2 gave stilbene-based azo dyes containing two M or 6-AM units, respectively. Diazotization of 5-(p-aminophenyl)-10,15,20-triphenylporphyrin and subsequent azo coupling of the diazoniun salt with M and with 6-AM was our route to get highly fluorescent morphine dyes. The resulting dyes can exist in two

  化学标记的适用策略 描述了使用重氮盐的吗啡（M）和6-乙酰基吗啡（6-AM）。M或6-AM与芳基重氮盐偶合，得到吗啡偶氮染料。所述耦合重氮化的M或6-AM比例为1：2的4,4'-二氨基二苯乙烯得到分别含有两个M或6-AM单元的基于二苯乙烯的偶氮染料。重氮化的5-（对氨基苯基）-10,15,20-三苯基卟啉以及随后将重氮盐与M和6-AM偶氮偶合是获得高荧光吗啡的途径染料。所得的染料可以以两种可能的互变异构结构存在，即偶氮和by，它们通过分子内的H键稳定在很大的程度上。结果表明，这些染料主要或仅以形式存在。该结论是由于在吸收光谱的380–420 nm区域（观察到偶氮形式的长波长吸收带的区域）中没有明显的谱带以及氘代DMSO中的NMR研究结果而得出的。 。通过在B3LYP / 6-31G *和B3LYP / 6-31G **水平上的密度泛函计算来判断化合物的互变异构性质。使用紫外荧光光电二极管阵
• Sulfate esters of morphine derivatives: Synthesis and characterization
  作者：András Váradi、András Gergely、Szabolcs Béni、Péter Jankovics、Béla Noszál、Sándor Hosztafi

  DOI：10.1016/j.ejps.2010.10.007

  日期：2011.1

  of sulfation with pyridine-SO(3) complex and sulfuric acid/N,N'-dicyclohexylcarbodiimide. Complete (1)H- and (13)C-NMR assignments are given for each of the synthesized compounds based on one- and two-dimensional homo- and heteronuclear measurements. Comparative analysis of chiral properties by circular dichroism and optical rotatory dispersion revealed characteristic differences in the spectra due

  通过吡啶-SO（3）络合物和硫酸/ N，N'-二环己基碳二亚胺的硫酸盐化反应，合成了十六种吗啡，可待因的3-O-和6-O-硫酸酯及其一些N-甲基季衍生物。基于一维和二维同核和异核测量，为每个合成的化合物给出了完整的（1）H-和（13）C-NMR分配。通过圆二色性和旋光色散对手性进行的比较分析表明，由于水溶液中强氢键的电荷，极性和分子内缔合的变化，光谱特征存在差异。将合成的硫酸酯是缺乏中央副作用潜在周止痛药，并且也作为用于涉及硫酸酯代谢物的各种分析研究参考物质是有用的。
• 6-O-Glycosylation of Morphine Derivatives Using Thioglycosides as Glycosyl Donors
  作者：Igor Rukhman、Lev Yudovich、Gennadiy Nisnevich、Arie L. Gutman

  DOI：10.1055/s-2000-6413

  日期：——

  A novel approach was developed for the synthesis of the pharmaceutically important morphine and dihydromorphine 6-β-d-glucuronides. The key step involves a selective 6-O-glycosylation of 3-O-protected morphines and dihydromorphines with thioglycosides that serve as glycosyl donors in the presence of thiophilic promoters. This novel approach may be useful for the O-glycosylation of other alkaloid derivatives.

  针对合成在医药领域重要的吗啡和二氢吗啡-6-β-d-葡萄糖醛酸苷，开发了一种新颖的方法。关键步骤包括在硫亲和助推剂存在下，利用硫代糖苷作为糖基供体，对3-O-保护的吗啡和二氢吗啡进行选择性的6-O-糖基化反应。这一新颖方法可能对其他生物碱衍生物的O-糖基化具有应用价值。