tert-butyl (2S,3S)-3-(tertbutyldimethylsilyloxy)-4-hydroxy-1-phenylbutan-2-ylcarbamate | 1174892-46-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (2S,3S)-3-(tertbutyldimethylsilyloxy)-4-hydroxy-1-phenylbutan-2-ylcarbamate
• 英文别名: tert-butyl N-[(2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 1174892-46-6
• 化学式: C₂₁H₃₇NO₄Si
• 分子量: 395.615
• InChiKey: XNDRYPGITKYAQO-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.51
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,3S)-3-(tertbutyldimethylsilyloxy)-4-hydroxy-1-phenylbutan-2-ylcarbamate 在 sodium carbonate 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以84%的产率得到(2S,3S)-3--2-<(tert-butyldimethylsilyl)oxy>-4-phenylbutanal
  参考文献：
  名称：

  A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of β-Secretase

  摘要：

  beta-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against beta-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce A beta(40) levels in plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led to the discovery of inhibitor 16 as a novel, potent, and orally efficacious BACE inhibitor.

  DOI：

  10.1021/ml3000148
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 在 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 四氢呋喃 为溶剂， 反应 14.17h， 以3.4 g的产率得到tert-butyl (2S,3S)-3-(tertbutyldimethylsilyloxy)-4-hydroxy-1-phenylbutan-2-ylcarbamate
  参考文献：
  名称：

  Stereoselective Synthesis ofanti-N-Protected 3-Amino-1,2-epoxides by Nucleophilic Addition toN-tert-Butanesulfinyl Imine of a Glyceraldehyde Synthon^†

  摘要：

  A di-O-TBS protected glyceraldellyde synthon was condensed with Ellman's reagent to form a bench-stable N-tert-butanesulfinyl imine 6, which served as a common intermediate for the stereoselective introduction Of various R groups. The Ellman adducts were converted to useful Multifunctional intermediates 18a-i in one pot. The alcohols 18a-i were efficiently elaborated to both known and novel anti-N-protected-3-amino-1,2-epoxides in two steps. Compound 2a is a key intermediate toward HIV protease inhibitors.

  DOI：

  10.1021/jo900643b

文献信息

• Stereoselective Synthesis of<i>anti</i>-<i>N</i>-Protected 3-Amino-1,2-epoxides by Nucleophilic Addition to<i>N</i>-<i>tert</i>-Butanesulfinyl Imine of a Glyceraldehyde Synthon^†
  作者：Scott S. Harried、Michael D. Croghan、Matthew R. Kaller、Patricia Lopez、Wenge Zhong、Randall Hungate、Paul J. Reider

  DOI：10.1021/jo900643b

  日期：2009.8.21

  A di-O-TBS protected glyceraldellyde synthon was condensed with Ellman's reagent to form a bench-stable N-tert-butanesulfinyl imine 6, which served as a common intermediate for the stereoselective introduction Of various R groups. The Ellman adducts were converted to useful Multifunctional intermediates 18a-i in one pot. The alcohols 18a-i were efficiently elaborated to both known and novel anti-N-protected-3-amino-1,2-epoxides in two steps. Compound 2a is a key intermediate toward HIV protease inhibitors.
• A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of β-Secretase
  作者：Matthew R. Kaller、Scott S. Harried、Brian Albrecht、Patricia Amarante、Safura Babu-Khan、Michael D. Bartberger、James Brown、Ryan Brown、Kui Chen、Yuan Cheng、Martin Citron、Michael D. Croghan、Russell Graceffa、Dean Hickman、Ted Judd、Chuck Kriemen、Daniel La、Vivian Li、Patricia Lopez、Yi Luo、Craig Masse、Holger Monenschein、Thomas Nguyen、Lewis D. Pennington、Tisha San Miguel、E. Allen Sickmier、Robert C. Wahl、Matthew M. Weiss、Paul H. Wen、Toni Williamson、Stephen Wood、May Xue、Bryant Yang、Jianhua Zhang、Vinod Patel、Wenge Zhong、Stephen Hitchcock

  DOI：10.1021/ml3000148

  日期：2012.11.8

  beta-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against beta-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce A beta(40) levels in plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led to the discovery of inhibitor 16 as a novel, potent, and orally efficacious BACE inhibitor.