cis-(+/-)-4-phenyl-3-triisopropylsilyloxy-1-(4-methoxyphenyl)azetidin-2-one

• 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: cis-(+/-)-4-phenyl-3-triisopropylsilyloxy-1-(4-methoxyphenyl)azetidin-2-one
• 英文别名: (3R,4S)-1-(4-methoxyphenyl)-4-phenyl-3-tri(propan-2-yl)silyloxyazetidin-2-one
• 化学式: C₂₅H₃₅NO₃Si
• 分子量: 425.643
• InChiKey: GZOMGOKQNVACJA-BJKOFHAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.34
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 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：

  cis-(+/-)-4-phenyl-3-triisopropylsilyloxy-1-(4-methoxyphenyl)azetidin-2-one 在 4-二甲氨基吡啶 、 ammonium cerium(IV) nitrate 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 4.83h， 生成 2'-epi 3'-epi N-debenzoyl N-tert-butoxycarbonyl taxol
  参考文献：
  名称：

  Synthesis of Docetaxel and Butitaxel Analogues through Kinetic Resolution of Racemic β-Lactams with 7-O-Triethylsilylbaccatin III

  摘要：

  The kinetic resolution of racemic cis-4-phenyl- and cis-4-tert-butyl-3-hydroxy-beta-lactam derivatives with 7-O-triethylsilylbaccatin III yielded paclitaxel and butitaxel analogues with high diastereoselectivity. The results demonstrated that the tert-butyldimethylsilyl protecting group at the C3-hydroxy group of the beta-lactams provided optimum kinetic resolution in comparison with the sterically less demanding triethylsilyl group and the larger triisopropylsilyl group. In addition, it was found that the C4 beta-lactam substituents also influenced diastereoselectivity. The C4 tert-butyl-beta-lactams provided better diastereoselectivity than the corresponding C4 phenyl beta-lactams.

  DOI：

  10.1021/jo061339s
• 作为产物：
  描述：

  3-acetoxy-N-(4-methoxyphenyl)-4-phenylazetidin-2-one 在 咪唑 、 四磷十氧化物 、 苯膦酸 、 氢气 、 nickel diacetate 、 碳酸氢钠 、 sodium carbonate 、 (3S,3'S,4S,4'S,11bS,11'bS)-(+)-4,4'-di-t-butyl-4,4',5,5'-tetrahydro-3,3'-bi-3H-dinaphtho[2,1-c:1',2'-e]phosphepin 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 80.0 ℃ 、6.0 MPa 条件下， 反应 36.0h， 生成 cis-(+/-)-4-phenyl-3-triisopropylsilyloxy-1-(4-methoxyphenyl)azetidin-2-one
  参考文献：
  名称：

  质子穿梭使镍催化的DKR催化α-酮基-β-内酰胺的不对称还原

  摘要：

  手性α-羟基-β-内酰胺是许多生物活性化合物和抗生素的关键片段，开发有效的合成方法具有重要价值。α-酮-β-内酰胺的高对映选择性动态动力学拆分（DKR）通过一种新颖的质子穿梭策略。Ni催化不对称氢化可有效地和对映选择性地还原各种α-酮-β-内酰胺，从而提供具有高收率和对映选择性的相应α-羟基-β-内酰胺衍生物（最高收率92％，最高收率94％ ee）。氘标记实验表明，苯基次膦酸通过促进烯醇化过程在α-酮-β-内酰胺的DKR中起关键作用。该方案的合成潜力通过其在紫杉酚和（+）- Epi -Cytoxazone关键中间体的合成中的应用得到证明。

  DOI：

  10.1039/d0cc05599a

文献信息

• New and efficient approaches to the semisynthesis of taxol and its C-13 side chain analogs by means of β-lactam synthon method
  作者：Iwao Ojima、Ivan Habus、Mangzhu Zhao、Martine Zucco、Young Hoon Park、Chung Ming Sun、Thierry Brigaud

  DOI：10.1016/s0040-4020(01)91210-4

  日期：1992.1

  Highly efficient chiral ester enolate-imine condensation giving 3-hydroxy-4-aryl-β-lactams with excellent enantiomeric purity is successfully applied to the asymmetric synthesis of the enantiomerically pure taxol C-13 side chain, N-benzoyl-(2R,3S)-3-phenyl-isoserine and its analogs. (3R,4S)-N-benzoyl-3-(1-ethoxyethoxy)-4-phenyl-2-azetidinone readily derived from the 3-hydroxy-4-phenyl-β-lactam is coupled

  高效手性酯烯酸酯-亚胺缩合可产生具有优异对映体纯度的3-羟基-4-芳基-β-内酰胺，已成功用于对映体纯紫杉醇C-13侧链N-苯甲酰基-（2 R， 3 S）-3-苯基-异丝氨酸及其类似物。易于衍生自3-羟基-4-苯基-β-内酰胺的（3 R，4 S）-N-苯甲酰基-3-（1-乙氧基乙氧基）-4-苯基-2-氮杂环丁酮与受保护的浆果赤霉素III偶联，然后通过脱保护得到光学纯的紫杉醇和高产率的10-脱乙酰基7,10-双（Troc）-紫杉醇。完全分配的1 H，13显示并讨论了由此合成的紫杉醇的C和2D（COSY和HETCOR）NMR光谱。
• New and efficient routes to norstatine and its analogs with high enantiomeric purity by β-Lactam Synthon Method
  作者：Iwao Ojima、Young Hoon Park、Chung Ming Sun、Thierry Brigaud、Mangzhu Zhao

  DOI：10.1016/0040-4039(92)89019-9

  日期：1992.9

  Norstatine and its analogs, i.e., 3-amino-2-hydroxyalkanoic acids, with high enantiomeric purity are obtained through effecient asymmetric synthesis of 3-silyloxy-β-lactams by chiral enolate - imine cyclocondensation, followed by hydrolysis.

  通过手性烯醇化物-亚胺环缩合，然后水解，有效地不对称合成3-甲硅烷氧基-β-内酰胺，可以得到具有高对映体纯度的Norstatine及其类似物，即3-氨基-2-羟基链烷酸。
• Extremely stereoselective alkylation of 3-siloxy-β-lactams and its applications to the asymmetric syntheses of novel 2-alkylisoserines, their dipeptides, and taxoids
  作者：Iwao Ojima、Tao Wang、Francette Delaloge

  DOI：10.1016/s0040-4039(98)00643-1

  日期：1998.5

  New and efficient synthetic routes to 2-alkylisoserines, their dipeptides and 2′-alkyl-taxoids were synthesized from enantiopure 3-alkyl-β-lactams 3 which were obtained through extremely distereoselective alkylation of β-lactams 2.

  从对映体纯的3-烷基-β-内酰胺3合成了2-烷基异丝氨酸，其二肽和2'-烷基-类紫杉醇的新型有效合成路线，所述对映纯的3-烷基-β-内酰胺3是通过对β-内酰胺2的极度立体选择性烷基化而获得的。
• Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells
  作者：Iwao Ojima、Cecilia L Fumero-Oderda、Scott D Kuduk、Zhuping Ma、Fumiko Kirikae、Teruo Kirikae

  DOI：10.1016/s0968-0896(03)00181-0

  日期：2003.7

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Asymmetric Mannich-Type Addition of Lithium Glycolates to Imines Producing 3-Hydroxy-4-phenylazetidin-2-ones
  作者：Kiyoshi Tomioka、Hiroki Fujieda、Seiji Hata、Ken-ichi Yamada

  DOI：10.3987/com-05-s(k)40

  日期：——