(S)-4-苄基-2-氮杂环丁酮 | 211618-76-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: (S)-4-苄基-2-氮杂环丁酮
• 英文名称: 4S-benzylazetidin-2-one
• 英文别名: (S)-4-benzylazetidin-2-one；(S)-4-benzyl-2-azetidinone；4(S)-benzylazetidin-2-one；(4S)-4-benzylazetidin-2-one
• CAS: 211618-76-7
• 化学式: C₁₀H₁₁NO
• 分子量: 161.203
• InChiKey: XQQADMLPVLHSPI-VIFPVBQESA-N

物化性质

• 沸点：
  350.4±11.0 °C(Predicted)
• 密度：
  1.136±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-4-苄基-2-氮杂环丁酮 在 盐酸 作用下， 反应 16.0h， 生成 β-homo-(S)-phenylalanine
  参考文献：
  名称：

  Burkholderia cepacia lipase and activated β-lactams in β-dipeptide and β-amino amide synthesis

  摘要：

  The work describes fluorine-activated and N-Boc-activated beta-lactams as acyl donors to N-nucleophiles in the presence of Burkholderia cepacia lipase (lipase PS-D). Fluorine activation at the beta-lactam ring causes the ring to open in high enantioselectivity and allows the preparation of beta-dipeptides and beta-amino amides. in the case of N-Boc-activation, the chemical ring opening is significant. beta-Dipeptide formation can then be considerably enhanced by the presence of lipase PS-D and/or by temperature. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2008.07.017
• 作为产物：
  描述：

  Z-Phe-O-COO-isoBu 在 palladium dihydroxide 氢气 、 silver benzoate 、 碳酸氢钠 、 甲基磺酰氯 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 乙腈 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 23.67h， 生成 (S)-4-苄基-2-氮杂环丁酮
  参考文献：
  名称：

  β-Lactam Derivatives as Inhibitors of Human Cytomegalovirus Protease

  摘要：

  The development of novel monobactam inhibitors of HCMV protease incorporating a carbon side chain at C-4 and a urea function at N-1 is described. Substitution with small groups at the C-3 position of the beta-lactam ring gave an increase in enzymatic activity and in stability; however, a lack of selectivity against other serine proteases was noted. The use of both tri- and tetrasubstituted urea functionalities gave effective inhibitors of HCMV protease. Benzyl substitution of the urea moiety was beneficial, especially when strong electron-withdrawing groups where attached at the para position. Modest antiviral activity was found in a plaque reduction assay.

  DOI：

  10.1021/jm980131z

文献信息

• Lipase-Involved Strategy to the Enantiomers of 4-Benzyl-β-Lactam as a Key Intermediate in the Preparation of β-Phenylalanine Derivatives
  作者：Xiang-Guo Li、Liisa T. Kanerva

  DOI：10.1002/adsc.200505253

  日期：2006.1

  A simple chemoenzymatic method for the preparation of the enantiomers of 4-benzyl-β-lactam (4-benzylazetidin-2-one) from allylbenzene has been described. The enantiomers of this key intermediate have been used to produce the corresponding enantiomers of β-phenylalanine and N-Boc-protected β-phenylalanine amide through the simple cleavage of the lactam ring by acid-catalyzed hydrolysis and by ammonolysis

  已经描述了一种从烯丙基苯制备4-苄基-β-内酰胺（4-苄基氮杂环丁烷-2-酮）对映异构体的简单化学酶促方法。该关键中间体的对映异构体已通过分别通过酸催化水解和通过氨解简单地裂解内酰胺环而用于生产相应的β-苯丙氨酸和N -Boc保护的β-苯丙氨酸酰胺的对映异构体。Burkholderia cepacia脂肪酶催化的动力学双分辨技术负责实现产品中的对映体纯度。这是通过酰化进行Ñ -hydroxymethylatedβ内酰胺，随后所得到的（的butanolysis小号）-酯。还研究了直接脂肪酶催化的β-内酰胺环的裂解。
• Azetidinone derivatives for the treatment of HCMV infections
  申请人：Boehringer Ingelheim (Canada) Ltd.

  公开号：US06242439B1

  公开（公告）日：2001-06-05

  A compound of formula I wherein R1 is hydrogen, methyl, ethyl, methoxy or methylthio; R2 and R3 each independently is hydrogen or lower alkyl; R4 is hydrogen, lower alkyl, methoxy, ethoxy or benzyloxy; R5 is lower alkyl, lower cycloalkyl, (CH2)mC(O)OR6 wherein m is the integer 1 or 2 and R6 is lower alkyl, phenyl optionally substituted; optionally Het or Het(lower alkyl); or R4 and R5 together with the nitrogen atom to which they are attached form a nitrogen containing ring optionally substituted with C(O)O-benzyl or with phenyl optionally substituted with C(O)OR7 wherein R7 is lower alkyl or (lower alkyl)phenyl; and Z is lower alkyl or optionally substituted phenyl or Het; with the proviso that when Z is (CH2)p-(Het), then R2 and R3 each is hydrogen; or a therapeutically acceptable acid addition salt thereof which compound is useful in the treatment of HCMV infections.

  式I的化合物中，其中R1为氢、甲基、乙基、甲氧基或甲硫基；R2和R3各自独立地为氢或较低的烷基；R4为氢、较低的烷基、甲氧基、乙氧基或苄氧基；R5为较低的烷基、较低的环烷基、(CH2)mC(O)OR6，其中m是整数1或2，R6为较低的烷基、苯基可选择地取代；可选择地为Het或Het(较低的烷基)；或者R4和R5与它们连接的氮原子一起形成一个含氮环，该环可选择地取代为C(O)O-苄基或苯基，该苯基可选择地取代为C(O)OR7，其中R7为较低的烷基或(较低的烷基)苯基；Z为较低的烷基或可选择地取代的苯基或Het；但是当Z为( )p-(Het)时，那么R2和R3各自为氢；或其治疗上可接受的酸盐，该化合物在HCMV感染的治疗中有用。
• [EN] AZETIDINONE DERIVATIVES FOR THE TREATMENT OF HCMV INFECTIONS<br/>[FR] DERIVES D'AZETIDINONE POUR LE TRAITEMENT D'INFECTIONS HCMV
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：WO1999018072A1

  公开（公告）日：1999-04-15

  (EN) A compound of formula (I) wherein R1 is hydrogen, methyl, ethyl, methoxy or methylthio; R2 and R3 each independently is hydrogen or lower alkyl; R4 is hydrogen, lower alkyl, methoxy, ethoxy or benzyloxy; R5 is lower alkyl, lower cycloalkyl, (CH2)mC(O)OR6 wherein m is the integer 1 or 2 and R6 is lower alkyl, phenyl optionally substituted; optionally Het or Het(lower alkyl); or R4 and R5 together with the nitrogen atom to which they are attached form a nitrogen containing ring optionally substituted with C(O)O-benzyl or with phenyl optionally substituted with C(O)OR7 wherein R7 is lower alkyl or (lower alkyl)phenyl; and Z is lower alkyl or optionally substituted phenyl or Het; with the proviso that when Z is (CH2)p-(Het), then R2 and R3 each is hydrogen; or a therapeutically acceptable acid addition salt thereof.(FR) L'invention concerne un composé de formule (I) dans laquelle R1 désigne un hydrogène, méthyle, éthyle, méthoxy ou méthylthio; R2 et R3, pris indépendamment, désignent l'hydrogène ou un alkyle C1-3; R4 désigne l'hydrogène, un alkyle inférieur, méthoxy, éthoxy ou benzyloxy; R5 désigne un alkyle inférieur, cycloalkyle inférieur, (CH2)mC(O)OR6 où m désigne le nombre entier 1 ou 2 et R6 désigne un alkyle inférieur, phényle éventuellement substitué; éventuellement Het ou Het(alkyle inférieur); ou R4 et R5 pris ensemble avec l'atome d'azote auquel ils sont liés forment un cycle renfermant un azote éventuellement substitué par C(O)O-benzyle ou par phényle éventuellement substitué par C(O)OR7 où R7 désigne un alkyle inférieur ou (alkyle inférieur)phényle; et Z désigne un alkyle inférieur ou éventuellement phényle substitué ou Het; à condition que lorsque Z désigne (CH2)p-(Het), R2 et R3 désignent chacun un hydrogène; ou un de ses sels d'addition d'acide thérapeutiquement acceptable.

  化合物的化学式为(I)，其中R1为氢、甲基、乙基、甲氧基或甲硫基；R2和R3各自独立地为氢或较低的烷基；R4为氢、较低的烷基、甲氧基、乙氧基或苄氧基；R5为较低的烷基、较低的环烷基、(CH2)mC(O)OR6，其中m为整数1或2，R6为较低的烷基、苯环可选地取代；可选地为Het或Het(较低的烷基)；或者R4和R5与它们所连接的氮原子一起形成含氮环，该环可选地取代为C(O)O-苄基或可选地取代为C(O)OR7的苯环，其中R7为较低的烷基或(较低的烷基)苯基；Z为较低的烷基或可选地取代的苯基或Het；但是当Z为( )p-(Het)时，R2和R3各自为氢；或其治疗上可接受的酸盐。
• Intramolecular hydroamidation of alkenes enabling asymmetric synthesis of β-lactams via transposed NiH catalysis
  作者：Xiang Lyu、Changhyeon Seo、Hoimin Jung、Teresa Faber、Dongwook Kim、Sangwon Seo、Sukbok Chang

  DOI：10.1038/s41929-023-01014-2

  日期：——

  through the use of readily accessible alkenyl dioxazolone derivatives. The reaction transcends the conventional NiH operation mode via a transposed mechanism initiated by N-activation, thus allowing for proximal C–N bond formation with excellent regioselectivity, regardless of the electronic properties of substituents. This mechanistic platform is also highly effective for the enantioselective intramolecular

  构建对映体富集的 β-内酰胺的合成方法非常有价值，因为它们在生物活性化合物中普遍存在，尤其是在青霉素和碳青霉烯类等抗生素中。β,γ-不饱和酰胺的分子内加氢酰胺化将为达到这一诱人的化学空间提供一种便捷的方法，但由于与形成应变四元环相关的困难而产生的区域选择性问题，它仍然受到限制。在这里，我们描述了一种 NiH 催化策略，通过使用易于获得的烯基二恶唑酮衍生物来解决这一挑战。该反应通过由N激活引发的转置机制超越了传统的NiH操作模式，从而允许以优异的区域选择性形成近端C-N键，而不管取代基的电子特性如何。
• Inhibition of Human Cytomegalovirus Protease by Monocyclic β-Lactam Derivatives:  Kinetic Characterization Using a Fluorescent Probe
  作者：Pierre R. Bonneau、Firoz Hasani、Céline Plouffe、Eric Malenfant、Steve R. LaPlante、Ingrid Guse、William W. Ogilvie、Raymond Plante、Walter C. Davidson、Jerry L. Hopkins、Maurice M. Morelock、Michael G. Cordingley、Robert Déziel

  DOI：10.1021/ja983905+

  日期：1999.4.1

  Recent reports have demonstrated the potential of monocyclic beta-lactam derivatives as inhibitors of human cytomegalovirus (HCMV) protease. Investigation of the mechanism of inhibition by NMR and mass spectrometry has revealed the presence of an acylenzyme intermediate suggesting that beta-lactams are hydrolyzed by the enzyme and cause inhibition by competing with substrate. The potential of a fluorogenic beta-lactam derivative for convenient kinetic characterization of this mechanism has been evaluated using 4S-(4methylumbelliferone)-3R-methylazetidin-2-one-1-carboxylic acid (4-methylpyridyl) amide (1). Upon acylation of the enzyme, the fluorescent umbelliferone moiety is released, allowing for continuous monitoring of the hydrolytic process. Examination of a series of progress curves by numerical analysis has provided valuable information on acylation and deacylation rates which relate to the IC50 values observed for beta-lactams. More importantly the potential of compound 1 as an active site titrating agent for HCMV protease has been exploited, and a simple protocol for rapid determination of active enzyme is described. The data are consistent with the HCMV protease dimer being composed of two functional active sites. This titrating agent represents an important tool that should significantly facilitate the characterization of this novel enzyme.