(3S,4S)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-carboxyethyl>azetidin-2-one | 97101-07-0

• 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,4S)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-carboxyethyl>azetidin-2-one
• 英文别名: 2(S)-<(3S,4R)-3<1(R)-<(tert-butyldimethylsilyl)oxy>ethyl>-2-oxoazetidin-4-yl>propanoic acid；(3S,4S)-3-<(R)-1-(t-Butyldimethylsilyloxy)ethyl>-4-<(S)-1-carboxyethyl>-2-azetidinone；(3S,4S)-[(R)-1'-((tert-butyldimethylsilyl)oxy)ethyl]-4-[(S)-1-carboxyethyl]-2-azetidinone；(3S,4S)-3-[(1'R)-1'-(tert-butyldimethylsilyloxy)ethyl]-4-[1'-carboxyethyl]azetidin-2-one；(3S,4S)-3-[(R)-1-(t-Butyldimethylsilyloxy)ethyl]-4-((S)-1-carboxyethyl)-2-azetidinone；(2S)-2-[(2S,3S)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-yl]propanoic acid
• CAS: 97101-07-0
• 化学式: C₁₄H₂₇NO₄Si
• 分子量: 301.458
• InChiKey: NNANGMFTFSNDLW-LNFKQOIKSA-N

物化性质

• 沸点：
  424.4±10.0 °C(Predicted)
• 密度：
  1.050±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.23
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4S)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-carboxyethyl>azetidin-2-one 在 4-二甲氨基吡啶 、 potassium carbonate 、 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 为溶剂， 反应 0.02h， 生成 (3S,4S)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-(methoxycarbonyl)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：

  4-乙酰氧基氮杂环丁酮 在 palladium diacetate 甲酸 、 sodium hydride 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (3S,4S)-3-<(1R)-1-<(tert-Butyldimethylsilyl)oxy>ethyl>-4-<(1S)-1-carboxyethyl>azetidin-2-one
  参考文献：
  名称：

  使用钯配合物通过脱氧烯丙氧基羰基化简单且高度非对映选择性地合成1β-甲基卡巴培南关键中间体

  摘要：

  通过钯催化的丙二烯丙基丙二酸酯衍生物4a的钯催化的脱烯丙氧羰基化反应，可以轻松地完成关键的1β-甲基卡巴培南中间体1的简单，非对映选择性合成，这很容易从（3S，4R）-4-acetoxy-3-[[R）-1 -（叔丁基二甲基甲硅烷氧基）乙基] -2-氮杂环丁酮2分两个步骤。

  DOI：

  10.1016/0040-4039(94)85196-4

文献信息

• Structure-activity relationships in the 2-arylcarbapenem series. Synthesis of 1-methyl-2-arylcarbapenems
  作者：Ravindra Nath Guthikonda、L. D. Cama、M. Quesada、M. F. Woods、T. N. Salzmann、B. G. Christensen

  DOI：10.1021/jm00388a022

  日期：1987.5

  tert-butyldimethylsilyl esters of the azetidinones 6-8b served as the crucial synthons in the preparation of the potentially useful ylide pyridyl thio esters 18-20. These intermediates were utilized to synthesize a host of title carbapenems 25-30d, 32, and 49-53. The antimicrobial properties and DHP-I susceptibility of these carbapenems were studied with reference to thienamycin.

  氮杂环丁酮6-8b的不稳定的叔丁基二甲基甲硅烷基酯在制备潜在有用的内酯吡啶基硫代硫酯18-20中起关键的合成子作用。这些中间体被用来合成许多标题碳青霉烯25-30d，32和49-53。参照噻菌霉素研究了这些碳青霉烯类的抗菌特性和DHP-1敏感性。
• Decarboxylative Trifluoromethylation of Aliphatic Carboxylic Acids
  作者：Jacob A. Kautzky、Tao Wang、Ryan W. Evans、David W. C. MacMillan

  DOI：10.1021/jacs.8b02650

  日期：2018.5.30

  conversion of carboxylic acids to trifluoromethyl groups via the combination of photoredox and copper catalysis. This transformation tolerates a wide range of functionality including heterocycles, olefins, alcohols, and strained ring systems. To demonstrate the broad potential of this new methodology for late-stage functionalization, we successfully converted a diverse array of carboxylic acid-bearing

  在此，我们公开了一种通过光氧化还原和铜催化的组合将羧酸转化为三氟甲基的有效方法。这种转变可以容忍广泛的官能团，包括杂环、烯烃、醇和应变环系统。为了证明这种新方法在后期功能化方面的广泛潜力，我们成功地将各种含羧酸的天然产物和药物转化为相应的三氟甲基类似物。
• Syntheses of chiral intermediates of 1-β-methylcarbapenems: (3<i>S</i>,4<i>R</i>)-3-[1(<i>R</i>)-<i>tert</i>-butyldimethylsilyloxyethyl]-4-chloroazetidin-2-one and (3<i>S</i>,4<i>S</i>)-3-[1(<i>R</i>)-<i>tert</i>-butyldimethylsilyloxyethyl]-4-[1(<i>R</i>)-<i>tert</i>-butylthiocarbonylethyl]azetidin-2-one
  作者：Masaki Endo

  DOI：10.1139/v87-357

  日期：1987.9.1

  The 4-chloroazetidinone 10, a very reactive chiral intermediate for 1-β-methylcarbapenems (1b), was easily prepared and isolated as a solid crystalline compound from the corresponding sulfide 5. Another chiral intermediate (16d) bearing the 1-β-methyl moiety was prepared by stereoselective aldol type condensation of either azetidinone 4 or 10 with metal enolates 14 (R = S—Bu′, M = ZrCp₂Cl, [Formula: see text], and SnBr). The β/α ratios were 9:1, 3:1, 2:1 respectively.

  4-氯吡嗪酮10是1-β-甲基卡巴比林（1b）的非常活性手性中间体，可以从相应的硫醚5中轻松制备并分离为固体结晶化合物。另一个携带1-β-甲基基团的手性中间体（16d）是通过对吡嗪酮4或10与金属烯醇酸盐14（R = S—Bu'，M = ZrCp2Cl，[Formula: see text]和SnBr）的立体选择性醛缩反应制备的。β/α比例分别为9:1，3:1，2:1。
• A stereoselective synthesis of a key 1β-methylcarbapenem intermediate via a diastereoselective decarboxylation
  作者：Woo-Baeg Choi、Hywyn R.O. Churchill、Joseph E. Lynch、Andrew S. Thompson、Guy R. Humphrey、R.P. Volante、Paul J. Reider、Ichiro Shinkai

  DOI：10.1016/0040-4039(94)85197-2

  日期：1994.4

  -1-t-butyldimethylsilyloxy)ethyl]-2-azetidinone via a sequence involving coupling with 2,2,5-trimethyl-1,3-dioxan-4,6-dione , N-silylation, solvolysis of the methylmeldrum's acid moiety and a stereoselective acid catalyzed decarboxylation.

  由（3R，4R）-4-乙酰氧基-制备（3S，4S）-3 [（R）-1-（叔丁基二甲基甲硅烷氧基）乙基] -4-[（R）-1-羧乙基] -2-氮杂环丁酮。3 - [（R）-1-吨-butyldimethylsilyloxy）乙基] -2-氮杂环丁酮通过涉及与2,2,5-三甲基-1,3-二恶烷-4,6-二酮耦合的序列，ñ -silylation，溶剂分解甲基熔体的酸部分和立体选择性酸催化的脱羧反应。
• 2-Picolyl thioesters; a useful synthon for the preparation of 1-β-alkyl carbapenem intermediates
  作者：Alain Martel、Jean-Paul Daris、Carol Bachand、Jacques Corbeil、Marcel Menard

  DOI：10.1139/v88-248

  日期：1988.6.1

  In this study, a highly stereoselective preparation of (3S,4S)-3-[(1R)-1-tert-butyldimethylsilyloxyethyl]-4-[(1R)-1-carboxy-ethyl]-azetidin-2-one (2) is reported. It involves a Lewis acid mediated condensation of (3S,4R)-4-acetoxy-3-[(1R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-one (3) with simple O-silylenol ethers of thiopropionates. From all the examples reported in this paper the 2-picolyl thiopropionate or similar arrangements were found to be essential for this stereoselection. Finally, a mechanism involving chelation control seems to be operative.

  本研究报告了一种高度立体选择性的制备方法，用于制备(3S,4S)-3-[(1R)-1-叔丁基二甲基硅氧乙基]-4-[(1R)-1-羧乙基]-氮杂环戊二酮(2)。它涉及到(3S,4R)-4-乙酰氧基-3-[(1R)-1-叔丁基二甲基硅氧乙基]氮杂环戊二酮(3)与硫代丙酸酯的简单O-硅烯醇醚通过Lewis酸介导的缩合反应。从本文中所报道的所有示例中，2-哌啶基硫代丙酸酯或类似的排列方式被发现对于这种立体选择性是必不可少的。最后，一个涉及螯合控制的机制似乎是起作用的。