3-(_tbutyldimethylsilyl)oxymorphone | 96453-53-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 3-(_tbutyldimethylsilyl)oxymorphone
• 英文别名: 4,5α-epoxy-3-<(tert-butyldimethylsilyl)oxy>-6-oxo-14-hydroxy-17-metylmorphinan；3-<(tertbutyldimethylsilyl)oxy>-4,5α-epoxy-14-hydroxy-17-methylmorphinan-6-one；(4R,4aS,7aR,12bS)-9-((tert-butyldimethylsilyl)oxy)-4a-hydroxy-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one；(4R,4aS,7aR,12bS)-9-[tert-butyl(dimethyl)silyl]oxy-4a-hydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 96453-53-1
• 化学式: C₂₃H₃₃NO₄Si
• 分子量: 415.605
• InChiKey: IPNYYCOMDDPEQI-XEDHWARRSA-N

物化性质

• 熔点：
  140-141 °C
• 沸点：
  507.2±50.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(_tbutyldimethylsilyl)oxymorphone 在 盐酸 、 硫酸 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 79.5h， 生成 14-羟基二氢降吗啡酮盐酸盐
  参考文献：
  名称：

  An improved synthesis of noroxymorphone

  摘要：

  A brief synthesis of noroxymorphone is described which involves the oxidation of 3-O-(t)butyldimethylsilylmorphine by manganese dioxide. The initial product is the corresponding morphinone which is further oxidised to the 14-hydroxymorphinone. After hydrogenation the 7,8-dihydro-14-hydroxymorphinone is acetylated and N-demethylation of the 14-O-acetylated product is achieved using vinyl chloroformate as the reagent. The overall yield from morphine is 40-45%.

  DOI：

  10.1016/s0040-4020(01)80016-8
• 作为产物：
  描述：

  3-(butyldimethylsilyl)morphine 在 palladium on activated charcoal manganese(IV) oxide 、 氢气 、 silica gel 作用下， 以 乙醇 、 氯仿 为溶剂， 25.0~40.0 ℃ 、101.33 kPa 条件下， 反应 5.33h， 生成 3-(_tbutyldimethylsilyl)oxymorphone
  参考文献：
  名称：

  An improved synthesis of noroxymorphone

  摘要：

  A brief synthesis of noroxymorphone is described which involves the oxidation of 3-O-(t)butyldimethylsilylmorphine by manganese dioxide. The initial product is the corresponding morphinone which is further oxidised to the 14-hydroxymorphinone. After hydrogenation the 7,8-dihydro-14-hydroxymorphinone is acetylated and N-demethylation of the 14-O-acetylated product is achieved using vinyl chloroformate as the reagent. The overall yield from morphine is 40-45%.

  DOI：

  10.1016/s0040-4020(01)80016-8

文献信息

• METHODS AND COMPOSITIONS FOR PREVENTING OPIOID ABUSE
  申请人：Waterville Valley Technologies, Inc.

  公开号：US20160326182A1

  公开（公告）日：2016-11-10

  Abuse-resistant opioid compounds, drug delivery systems, pharmaceutical compositions comprising an opioid covalently bound to a chemical moiety are provided. Methods of delivering an active ingredient to a subject and methods of preventing opioid abuse are also provided.

  提供了耐滥用的阿片类化合物、药物输送系统、含有阿片类药物与化学基团共价结合的制药组合物。还提供了将活性成分输送给受试者的方法以及预防阿片类药物滥用的方法。
• The facility of formation of a .DELTA.6 bond in dihydromorphinone and related opiates
  作者：Hiroshi Nagase、Akira Abe、Philip S. Portoghese

  DOI：10.1021/jo00278a025

  日期：1989.8
• Opioid agonists and antagonists. 6-Desoxy-6-substituted lactone, epoxide, and glycidate ester derivatives of naltrexone and oxymorphone
  作者：Gary A. Koolpe、Wendel L. Nelson、T. L. Gioannini、Lloyd Angel、Nicholas Appelmans、Eric J. Simon

  DOI：10.1021/jm00145a018

  日期：1985.7

  Synthesis and opioid radioreceptor assay data on analogues closely related to 6-desoxy-6-spiro-alpha-methylene-gamma-lactone 5a, a compound with irreversible activity in this assay, are reported. Saturated lactones (7a,b), endocyclic alpha, beta-unsaturated gamma-lactones (8a,b and 9a), and 6 alpha,7 alpha-fused alpha-methylene-gamma-lactones (10a and 11a) were prepared. Related 6-desoxy-6-methylene 6 beta- and 6 alpha-oxides (12a,b and 13a) and glycidate esters 14a,b and 15a,b were also prepared with use of naltrexone (1a) and oxymorphone (1b) as starting material. Compounds in the N-cyclopropylmethyl (N-CPM) series were more potent than those in the N-Me series in displacing [3H]naltrexone in the opioid radioreceptor assay, usually by 2-16-fold in the absence of Na ion. The most potent N-CPM analogues were epoxides 12a and 13a and glycidate esters 14a and 15a, showing IC50's of 2-6 nM, similar to that of 5a. Of the N-Me analogues, 6 beta-oxide 12b was most active, with an IC50 of 8 nM in the absence of Na ion. For the N-CPM analogues, the Na ion ratios were generally less than 1, with two exceptions. The N-Me analogues showed expected larger Na ion effects of 7 or greater. None of the lactone analogues had irreversible effects when preincubated in the rat brain membrane preparation, even at 37 degrees C for 30 min, i.e., washing restored [3H]naltrexone binding to control levels. These results clearly show that the alpha-methylene-gamma-lactone moiety of 5a is required for irreversible effects, consistent with it serving as a conjugate addition acceptor of a nucleophilic group from a ligand at or near the receptor. The epoxides and glycidate esters also had no irreversible activity, indicating more electrophilic functional groups are needed and/or these electrophiles are not properly aligned to react with nucleophilic groups at or near the opioid receptor.
• NAGASE, HIROSHI;ABE, AKIRA;PORTOGHESE, PHILIP S., J. ORG. CHEM., 54,(1989) N7, C. 4120-4125
  作者：NAGASE, HIROSHI、ABE, AKIRA、PORTOGHESE, PHILIP S.

  DOI：——

  日期：——
• An improved synthesis of noroxymorphone
  作者：Aleyamma Ninan、Malcolm Sainsbury

  DOI：10.1016/s0040-4020(01)80016-8

  日期：1992.1

  A brief synthesis of noroxymorphone is described which involves the oxidation of 3-O-(t)butyldimethylsilylmorphine by manganese dioxide. The initial product is the corresponding morphinone which is further oxidised to the 14-hydroxymorphinone. After hydrogenation the 7,8-dihydro-14-hydroxymorphinone is acetylated and N-demethylation of the 14-O-acetylated product is achieved using vinyl chloroformate as the reagent. The overall yield from morphine is 40-45%.