(3R,4S)-3-TBDMS-O-4-phenyl-2-azetidinone | 132127-30-1

• 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: (3R,4S)-3-TBDMS-O-4-phenyl-2-azetidinone
• 英文别名: (3R,4S)-3-tert-Butyldimethylsilyloxy-4-phenylazetidin-2-one；(3R,4S)-3-<(tert-butyldimethylsilyl)oxy>-4-phenylazetidin-2-one；(3R,4S)-3-tert-butyldimethylsiloxy-4-phenylazetidin-2-one；(3R,4S)-4-phenyl-3-tert-butyldimethylsilyloxyazetidin-2-one；(3R,4S)-3-[tert-butyl(dimethyl)silyl]oxy-4-phenylazetidin-2-one
• CAS: 132127-30-1
• 化学式: C₁₅H₂₃NO₂Si
• 分子量: 277.439
• InChiKey: XSLAYGYEDULIRR-QWHCGFSZSA-N

物化性质

• 熔点：
  108-110 °C
• 沸点：
  382.7±42.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3R,4S)-3-TBDMS-O-4-phenyl-2-azetidinone 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以90%的产率得到(3R,4S)-3-羟基-4-苯基-2-氮杂环丁酮
  参考文献：
  名称：

  Asymmetric synthesis of 3-amino-2-hydroxyalkanoates by Mannich reaction of menthyl acetate with imines and subsequent oxidation

  摘要：

  Lithium amide-assisted Mannich-type reaction of menthyl acetate-derived lithium enolate with PMP-arylaldimines and subsequent in situ oxidation with oxaziridine gave syn-3-amino-3-aryl-2-hydroxypropanoates with high syn-selectivity and diastereoselectivity (with respect to menthyl moiety) in a one-pot procedure. Propargyl aldehyde-derived imines were also stereoselectively converted to the Mannich-oxidation products by a stepwise procedure. (c) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2007.05.031
• 作为产物：
  描述：

  4-methoxy-N-[(E)-phenylmethylidene]aniline 在 咪唑 、 ammonium cerium(IV) nitrate 、 甲基溴化镁 、 水 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 (3R,4S)-3-TBDMS-O-4-phenyl-2-azetidinone
  参考文献：
  名称：

  Asymmetric synthesis of 3-amino-2-hydroxyalkanoates by Mannich reaction of menthyl acetate with imines and subsequent oxidation

  摘要：

  Lithium amide-assisted Mannich-type reaction of menthyl acetate-derived lithium enolate with PMP-arylaldimines and subsequent in situ oxidation with oxaziridine gave syn-3-amino-3-aryl-2-hydroxypropanoates with high syn-selectivity and diastereoselectivity (with respect to menthyl moiety) in a one-pot procedure. Propargyl aldehyde-derived imines were also stereoselectively converted to the Mannich-oxidation products by a stepwise procedure. (c) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2007.05.031

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。
• Syntheses and Structure−Activity Relationships of Taxoids Derived from 14β-Hydroxy-10-deacetylbaccatin III
  作者：Iwao Ojima、John C. Slater、Scott D. Kuduk、Craig S. Takeuchi、Rayomand H. Gimi、Chung-Ming Sun、Young Hoon Park、Paula Pera、Jean M. Veith、Ralph J. Bernacki

  DOI：10.1021/jm960563e

  日期：1997.1.1

  A series of new taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III was synthesized by means of the beta-lactam synthon method. Most of the new taxoids thus synthesized possess excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines, and several of these taxoids show subnanomolar IC50 values which are severalfold

  通过β-内酰胺合成子法合成了一系列衍生自14个β-羟基-10-去乙酰基浆果赤霉素III的新的类紫杉醇。如此合成的大多数新类紫杉醇对人卵巢（A121），非小细胞肺癌（A549），结肠（HT-29）和乳腺癌（MCF-7）癌细胞系均具有出色的细胞毒性，其中一些类紫杉醇显示的亚纳摩尔IC50值比紫杉醇和多西紫杉醇好几倍至1个数量级。3'-和3'-N位置的修饰对活性产生显着影响。对于C-3'处的取代基，细胞毒性以2-呋喃基约2-甲基-1-丙烯基>或= 2-甲基丙基>（E）-1-丙烯基>或=正丙基>苯基>>的顺序降低2，2-二甲基丙基。对于3'-N取代基，活性按照t-BuOCO> Ph>正己酰基的顺序降低。通过适当修饰C-10上的取代基，可以观察到对表达多药耐药性（MDR）表型的耐阿霉素的人乳腺癌细胞MCF7-R的细胞毒性显着增加。在C-10处观察到的取代基对MCF7-R活性的显着影响可归因于有效抑制
• The Effect of the Aromatic Rings of Taxol on Biological Activity and Solution Conformation: Synthesis and Evaluation of Saturated Taxol and Taxotere Analogs
  作者：Thomas C. Boge、Richard H. Himes、David G. Vander Velde、Gunda I. Georg

  DOI：10.1021/jm00046a018

  日期：1994.9

  (triethylsilyl)baccatin III. The taxol analogue 15, in which all three taxol phenyl groups are substituted by a cyclohexyl moiety, was synthesized in one step from taxol via hydrogenation. All three analogues (9, 14, and 15) exhibited strong activity in the microtubule assembly assay and cytotoxicity comparable to taxol against B16 melanoma cells. It was also shown that 9, like taxol and taxotere, has an extended

  详细的紫杉醇和紫杉醇的新型环己基类似物的合成和生物学评价。由浆果赤霉素III通过氢化制备2-（环己基羰基）-2-脱苯甲酰基浆果赤霉素III（6）。随后将6与Nt-BOC-3-[（叔丁基二甲基甲硅烷基）氧基] -4-苯基-2-氮杂环丁酮（7）偶联，然后除去保护基，得到2-（环己基羰基）-2-脱苯甲酰基紫杉醇（ 9）。以类似的合成顺序，由N-苯甲酰基-3-[（叔丁基二甲基甲硅烷基）氧基] -4-环己基-2-氮杂环丁酮（12）和（三乙基甲硅烷基）制得3'-环己基-3'-去苯紫杉醇（14）。浆果赤霉素III。由紫杉醇经氢化一步合成了紫杉醇类似物15，其中所有三个紫杉醇苯基均被环己基部分取代。所有三个类似物（9、14，15）在微管组装试验中表现出很强的活性，并具有与紫杉醇相当的针对B16黑色素瘤细胞的细胞毒性。还显示9，像紫杉醇和紫杉醇一样，在氯仿中具有延伸的侧链，但是在DMSO /水混合物中优选采
• A highly efficient route to taxotere by the β-Lactam Synthon Method
  作者：Iwao Ojima、Chung Ming Sun、Martine Zucco、Young Hoon Park、Olivier Duclos、Scott Kuduk

  DOI：10.1016/s0040-4039(00)60514-2

  日期：1993.6

  Taxotere, a highly promising anticancer drug, is synthesized through an efficient coupling of 7,10-diTroc-10-deacetylbaccatin III with enantiomerically pure (3R,4S)-1-(t)BOC-3-EEO-4-phenylazetidin-2-one which is obtained via chiral ester enolate - imine cyclocondensation.
• Efficient and practical asymmetric synthesis of the taxol C-13 side chain, N-benzoyl-(2R,3S)-3-phenylisoserine, and its analogs via chiral 3-hydroxy-4-aryl-.beta.-lactams through chiral ester enolate-imine cyclocondensation
  作者：Iwao Ojima、Ivan Habus、Mangzhu Zhao、Gunda I. Georg、Lalith R. Jayasinghe

  DOI：10.1021/jo00005a003

  日期：1991.3

  A highly efficient chiral ester enolate-imine condensation giving 3-hydroxy-4-aryl-beta-lactams with > 96% ee is successfully applied to the asymmetric synthesis of the enantiomerically pure taxol C-13 side chain, N-benzoyl-(2R,3S)-3-phenylisoserine, and its analogues.