(3S)-1-(4-methoxyphenyl)-[(1R)-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one | 141805-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (3S)-1-(4-methoxyphenyl)-[(1R)-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one
• 英文别名: (3S)-3-{(1R)-1-[(tert-Butyldimethylsilyl)oxy]ethyl}-1-(4-methoxyphenyl)azetidin-2-one；(3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-1-(4-methoxyphenyl)azetidin-2-one
• CAS: 141805-92-7
• 化学式: C₁₈H₂₉NO₃Si
• 分子量: 335.519
• InChiKey: OWNDXWGMCDXEAF-CJNGLKHVSA-N

物化性质

• 沸点：
  448.006±20.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.037±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S)-1-(4-methoxyphenyl)-[(1R)-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one 在 (NH₄)2Ce(NO₃)3 作用下， 以 水 、 乙腈 为溶剂， 反应 0.33h， 以67%的产率得到(1'R,3S)-3-<1'-<(tert-butyldimethylsilyl)oxy>ethyl>azetidin-2-one
  参考文献：
  名称：

  .beta.-Lactams. 3. Asymmetric total synthesis of new non-natural 1.beta.-methylcarbapenems exhibiting strong antimicrobial activities and stability against human renal dehydropeptidase-I

  摘要：

  Asymmetric synthesis of 11, the precursor to chiral (3R,4R)-3-[(1R)-1-[(tert-butyldimethylsilyl)oxy]ethyl]-4-acetoxyazetidin-2-one (3) was achieved by utilizing a highly diastereoselective aldol-type reaction of acetaldehyde and the chiral tin(II) enolate of 5. Similar diastereoselective alkylations of chiral and achiral tin(II) enolates 13a-d with chiral 3 were also performed to obtain the desired alkylated azetidin-2-ones (17a-d). Compounds 17a,b were successfully converted to new, non-natural 1-beta-methylcarbapenems 1a and 1b, which exhibited strong and wide-ranging antimicrobial activities and excellent stability against human renal dehydropeptidase-I.

  DOI：

  10.1021/jo00041a033
• 作为产物：
  描述：

  3-(R)-t-butyldimethylsilyloxybutanoic acid 在 草酰氯 、 三氟化硼乙醚 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.25h， 生成 (3S)-1-(4-methoxyphenyl)-[(1R)-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one
  参考文献：
  名称：

  实用合成用于生产β-内酰胺抗生素的关键中间体

  摘要：

  N-（对甲氧基苯基）-六氢-1,3,5-三嗪在路易斯酸和（R）-3-（叔丁基二甲基甲硅烷氧基）丁酰氯与Et 3 N的存在下直接提供（3 S，1' [R ）- ñ - p -甲氧基苯基-3-（1-吨-butyldimethylsilyloxy）乙基氮杂-2-酮与良好非对映选择性。该产物被转化为4-乙酰氧基-氮杂环丁酮1，这是合成β-内酰胺类抗生素的关键中间体。

  DOI：

  10.1016/s0040-4039(98)01700-6

文献信息

• SAR and LC/MS Studies of β-Lactamic Inhibitors of Human Fatty Acid Amide Hydrolase (<i>h</i>FAAH): Evidence of a Nonhydrolytic Process
  作者：Marion Feledziak、Giulio G. Muccioli、Didier M. Lambert、Jacqueline Marchand-Brynaert

  DOI：10.1021/jm200723m

  日期：2011.10.13

  The endocannabinoid hydrolyzing enzyme FAAH uses a nonclassical catalytic triad (namely, Ser-Ser-Lys instead of Ser-Asp-His) to cleave its endogenous substrates. Because inhibiting FAAH has a clear therapeutic potential, we previously developed beta-lactam-type inhibitors of hFAAH. Here, we report the synthesis of five novel derivatives (5-9) of our lead compound 1-(pent-4-enoyl)-3 (S)-[1(R)-(4-phenylbutanoyloxy)-ethyl] azetidin-2-one (4, IC50 = 5 nM) obtained via the systematic replacement of one to three carbonyls by methylene groups. The SAR results showed that the imide, but not the lactam, function is essential to the inhibition of hFAAH. We also performed LC/MS analysis following incubation of our inhibitors with hFAAH or mouse liver. We demonstrated that hFAAH interacts with these beta-lactam-type inhibitors but, unexpectedly, does not open the beta-lactam moiety. This mechanism seems to be unique to FAAH because the beta-lactam function of the inhibitors is hydrolyzed when they are incubated in the presence of the serine hydrolases expressed in the mouse liver. Finally, we confirmed these results by showing that a highly selective FAAH inhibitor (PF-750) does not prevent this hydrolysis by liver homogenates.
• .beta.-Lactams. 3. Asymmetric total synthesis of new non-natural 1.beta.-methylcarbapenems exhibiting strong antimicrobial activities and stability against human renal dehydropeptidase-I
  作者：Yoshimitsu Nagao、Yunosuke Nagase、Toshio Kumagai、Hiroshi Matsunaga、Takao Abe、Osamu Shimada、Takaaki Hayashi、Yoshinori Inoue

  DOI：10.1021/jo00041a033

  日期：1992.7

  Asymmetric synthesis of 11, the precursor to chiral (3R,4R)-3-[(1R)-1-[(tert-butyldimethylsilyl)oxy]ethyl]-4-acetoxyazetidin-2-one (3) was achieved by utilizing a highly diastereoselective aldol-type reaction of acetaldehyde and the chiral tin(II) enolate of 5. Similar diastereoselective alkylations of chiral and achiral tin(II) enolates 13a-d with chiral 3 were also performed to obtain the desired alkylated azetidin-2-ones (17a-d). Compounds 17a,b were successfully converted to new, non-natural 1-beta-methylcarbapenems 1a and 1b, which exhibited strong and wide-ranging antimicrobial activities and excellent stability against human renal dehydropeptidase-I.
• A practical synthesis of a key intermediate for the production of β-lactam antibiotics
  作者：Gianfranco Cainelli、Paola Galletti、Daria Giacomini

  DOI：10.1016/s0040-4039(98)01700-6

  日期：1998.10

  exahydro-1,3,5-triazine in presence of a Lewis acid and (R)-3-(t-butyldimethylsilyloxy)butyric acid chloride with Et3N directly furnish (3S,1′R)-N-p-methoxyphenyl-3-(1-t-butyldimethylsilyloxy)ethylazetidin-2-one with good diastereo-selectivity. This product is transformed into the 4-acetoxy-azetidinone 1, a key intermediate in the synthesis of β-lactam antibiotics.

  N-（对甲氧基苯基）-六氢-1,3,5-三嗪在路易斯酸和（R）-3-（叔丁基二甲基甲硅烷氧基）丁酰氯与Et 3 N的存在下直接提供（3 S，1' [R ）- ñ - p -甲氧基苯基-3-（1-吨-butyldimethylsilyloxy）乙基氮杂-2-酮与良好非对映选择性。该产物被转化为4-乙酰氧基-氮杂环丁酮1，这是合成β-内酰胺类抗生素的关键中间体。