(4S,5S)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-benzyl-5-formyl-1,3-oxazolidine | 174510-86-2

• 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: (4S,5S)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-benzyl-5-formyl-1,3-oxazolidine
• 英文别名: (4S,5S)-tert-butyl 4-benzyl-5-formyl-2,2-dimethyloxazolidine-3-carboxylate；tert-butyl (4S,5S)-4-benzyl-5-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 174510-86-2
• 化学式: C₁₈H₂₅NO₄
• 分子量: 319.401
• InChiKey: DAQUBMNBMKDYRN-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S,5S)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-benzyl-5-formyl-1,3-oxazolidine 在 氯化二乙基铝 、 magnesium sulfate 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (2S,3R,4S)-2-N-benzylhydroxylamine-4-tert-butoxycarbonylamino-1,5-diphenyl-4N,3O-isopropylidene-3-pentanol
  参考文献：
  名称：

  立体控制合成的HIV蛋白酶抑制剂的伪C 2对称的1,3-二氨基-2-丙醇核心单元

  摘要：

  伪C 2对称的二苄基二氨基醇（S，S）-1和两种内消旋立体异构体1a和1b（R = PhCH 2）的合成是通过将立体氯化苄基氯化镁加到衍生自手性β-氨基-的硝酮3中来进行的。依次从苯丙氨酸获得的α-羟基醛2；从N-Boc 1-苯丙氨酸得到的（S，S）-1的总产率为23％; 可以从相同的α-氨基醛的d-异构体开始，以类似的方式制备对映体（R，R）-1 。

  DOI：

  10.1016/s0040-4039(96)02355-6
• 作为产物：
  描述：

  2-<2(S)-(tert-Butoxyformamido)-1-hydroxy-3-phenylpropyl>thiazole 在 4-甲基苯磺酸吡啶 作用下， 以 甲苯 为溶剂， 反应 18.0h， 生成 (4S,5S)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-benzyl-5-formyl-1,3-oxazolidine
  参考文献：
  名称：

  Grignard Addition to Aldonitrones. Stereochemical Aspects and Application to the Synthesis of C₂-Symmetric Diamino Alcohols and Diamino Diols

  摘要：

  A new example of the stereoselective installation of the amino group at a saturated carbon center via organometallic addition of chiral aldehydes to nitrones is illustrated by the synthesis of 1,3-diamino propanol 1 and 1,4-diamino butandiol 2 units. Three diamino alcohol 1 stereotriads were obtained by stereoselective addition of alkylmagnesium halides (benzyl, cyclohexylmethyl, and metallyl) to the N-benzyl nitrones derived from beta-amino-alpha-hydroxy aldehydes followed by reduction of the resulting N-benzylhydroxylamines. Three 1,4-dibenzyl substituted stereoisomers of type 2 with fixed S configuration at C2 and C3 were prepared by sequential and simultaneous amination in two directions starting from L-threose nitrone and L-tartraldehyde bis-nitrone, respectively. The R,S,S,R isomer obtained by the former route was converted into a seven-membered ring cyclic urea (1,3-diazapin-2-one), i.e., a compound that belongs to a class of nonpeptide HIV-1 protease inhibitors.

  DOI：

  10.1021/jo980980u

文献信息

• A Template-Based Approach to Inhibitors of Calpain 2, 20S Proteasome, and HIV-1 Protease
  作者：Seth A. Jones、Paul M. Neilsen、Limei Siew、David F. Callen、Nathan E. Goldfarb、Ben M. Dunn、Andrew D. Abell

  DOI：10.1002/cmdc.201300387

  日期：2013.12

  Specificity counts: A template‐based approach to protease inhibitors is presented using a core macrocycle that presents a generic β‐strand template for binding to protease active sites. This is then specifically functionalized at P2, and the C and N termini to give inhibitors of calpain 2, 20S proteasome, and HIV‐1 protease.

  特异性计数：使用核心大环化合物提出了一种基于模板的蛋白酶抑制剂方法，该方法提供了与蛋白酶活性位点结合的通用β链模板。然后在P 2以及C和N末端将其特异性官能化，以提供钙蛋白酶2、20S蛋白酶体和HIV-1蛋白酶的抑制剂。
• Beta-secretase modulators and methods of use
  申请人：Zhong Wenge

  公开号：US20070185144A1

  公开（公告）日：2007-08-09

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A, B, W, R 3 , R 4 , R 5 , i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula I, or compositions including them, to a subject. The invention also comprises further embodiments of Formulas II and III, intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一类新型化合物，可用于调节β-分泌酶酶活性和治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一种实施方式中，化合物具有通式I，其中A、B、W、R3、R4、R5、i和j在此定义。本发明还包括包含一个或多个通式I化合物的药物组合物，以及使用这些化合物的方法，包括通过将通式I化合物或包含它们的组合物给予受试者治疗AD和相关疾病。本发明还包括通式II和III的进一步实施方式，以及用于制备本发明化合物的中间体和过程。
• BETA-SECRETASE MODULATORS AND METHODS OF USE
  申请人：Zhong Wenge

  公开号：US20100222338A1

  公开（公告）日：2010-09-02

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A, B, W, R 3 , R 4 , R 5 , i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula I, or compositions including them, to a subject. The invention also comprises further embodiments of Formulas II and III, intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一类新型化合物，可用于调节β-分泌酶酶活性和治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关疾病。在一种实施例中，该化合物具有一般式I，其中A、B、W、R3、R4、R5、i和j在此被定义。本发明还包括包含一种或多种I式化合物的制药组合物，以及使用这些化合物的方法，包括通过将I式化合物或包含它们的组合物用于治疗AD和相关疾病来给受试者施用。本发明还包括进一步的II式和III式的实施例，以及用于制备本发明化合物的中间体和方法。
• WO2007/61670
  申请人：——

  公开号：——

  公开（公告）日：——
• US7745484B2
  申请人：——

  公开号：US7745484B2

  公开（公告）日：2010-06-29