(2S,3S)-3--2-<(tert-butyldimethylsilyl)oxy>-4-phenylbutanal | 144944-04-7

• 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: (2S,3S)-3--2-<(tert-butyldimethylsilyl)oxy>-4-phenylbutanal
• 英文别名: (S,S)-3--2-<(tert-butyldimethylsilyl)oxy>-4-phenylbutanal；tert-butyl (2S,3S)-3-(tert-butyldimethylsilyloxy)-4-oxo-1-phenylbutan-2-ylcarbamate；tert-butyl (2S,3S)-3-(tert-butyldimethylsilyloxy)-4-oxo-1-phenylpent-4-en-2-ylcarbamate；tert-butyl N-[(2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-4-oxo-1-phenylbutan-2-yl]carbamate
• CAS: 144944-04-7
• 化学式: C₂₁H₃₅NO₄Si
• 分子量: 393.599
• InChiKey: UXLPIBKQWQYCAO-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.71
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3--2-<(tert-butyldimethylsilyl)oxy>-4-phenylbutanal 在 盐酸 、 三乙酰氧基硼氢化钠 、 原甲酸三甲酯 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 (2R,3S)-3-amino-1-((S)-6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridine]-4'-ylamino)-4-phenylbutan-2-ol
  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：

  [(1S,2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenyl-1-(1,3-thiazol-2-yl)propyl] acetate 在 咪唑 、 4-二甲氨基吡啶 、 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.25h， 生成 (2S,3S)-3--2-<(tert-butyldimethylsilyl)oxy>-4-phenylbutanal
  参考文献：
  名称：

  Chelation- and Non-chelation-Controlled Addition of 2-(Trimethylsilyl)thiazole to .alpha.-Amino Aldehydes: Stereoselective Synthesis of the .beta.-Amino-.alpha.-hydroxy Aldehyde Intermediate for the Preparation of the Human Immunodeficiency Virus Proteinase Inhibitor Ro 31-8959

  摘要：

  DOI：

  10.1021/jo00129a057

文献信息

• WO2007/62007
  申请人：——

  公开号：——

  公开（公告）日：——
• Regio- and Stereocontrolled Formation of Chiral Epoxy Oxazolidines via Bromocarbamation of <i>N</i>-Boc Alkenyl Oxazolidines. Application to Asymmetric Synthesis
  作者：Claude Agami、François Couty、Louis Hamon、Olivier Venier

  DOI：10.1021/jo962277g

  日期：1997.4.1

  Treatment of alpha-alkenyl N-Boc oxazolidines with N-bromosuccinimide leads to epoxy oxazolidines via a bromocyclocarbamation reaction which is completely stereoselective. Action of sodium azide an these epoxides, followed by a few functional group manipulations, eventually affords chiral beta-amino alcohols which are intermediates for the enantioselective synthesis of bioactive products: the anti side chain of taxol and a hydroxyethylamine isostere. Both the bromocarbamation cyclization and the nucleophilic cleavage of epoxides are totally regioselective. AM1 calculations suggest that this selectivity is controlled by the positive charge distribution at the electrophilic centers.
• Chelation- and Non-chelation-Controlled Addition of 2-(Trimethylsilyl)thiazole to .alpha.-Amino Aldehydes: Stereoselective Synthesis of the .beta.-Amino-.alpha.-hydroxy Aldehyde Intermediate for the Preparation of the Human Immunodeficiency Virus Proteinase Inhibitor Ro 31-8959
  作者：Alessandro Dondoni、Daniela Perrone、Pedro Merino

  DOI：10.1021/jo00129a057

  日期：1995.12
• 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.