(4S,5S)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-benzyl-5-formyl-1,3-oxazolidine | 134458-64-3

• 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: tert-butyl (4S,5R)-4-benzyl-5-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 134458-64-3
• 化学式: C₁₈H₂₅NO₄
• 分子量: 319.401
• InChiKey: DAQUBMNBMKDYRN-GJZGRUSLSA-N

物化性质

• 沸点：
  419.2±45.0 °C(Predicted)
• 密度：
  1.135±0.06 g/cm3(Predicted)

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 sodium tetrahydroborate 、 sodium sulfate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 tert-butyl (4S,5S)-4-benzyl-5-[[[(2S)-1-methoxy-4-methylsulfanyl-1-oxobutan-2-yl]amino]methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
  参考文献：
  名称：

  A Stereoselective Route to Hydroxyethylamine Dipeptide Isosteres

  摘要：

  An efficient synthesis of stereodefined hydroxyethylamine dipeptide isosteres has been developed, utilizing a syn-selective Grignard addition and reductive amination as the key reactions.

  DOI：

  10.1021/jo001072b
• 作为产物：
  描述：

  (2R,3S)-N-(tert-butoxycarbonyl)-3-amino-2-hydroxy-4-phenylbutanoic acid methyl ester 在 二异丁基氢化铝 、 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 生成 (4S,5S)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-benzyl-5-formyl-1,3-oxazolidine
  参考文献：
  名称：

  不对称氨基羟化反应在HIV蛋白酶抑制剂，羟乙烯二肽等排体和γ-氨基酸衍生物合成中的应用

  摘要：

  内酯1的对映选择性合成是（2 R，4 S，5 S）羟基亚乙基二肽等排物的前体和氨基酸AHPPA 2的合成，是通过使用Sharpless不对称氨基羟基化反应为关键步骤的常见中间体5完成的。

  DOI：

  10.1016/j.tetlet.2004.05.057

文献信息

• New approaches to the asymmetric synthesis of dipeptide isosteres via β-Lactam Synthon Method
  作者：Iwao Ojima、Hong Wang、Tao Wang、Edward W. Ng

  DOI：10.1016/s0040-4039(97)10677-3

  日期：1998.2

  New and efficient synthetic routes to dipeptide isosteres with high enantiomeric purity, e.g., hydroxyethylene, dihydroxyethylene and hydroxyethylamine isosteres, have been developed via oxiranes 6 and formyloxazolines 13 derived from N-t-Boc-β-lactams 4.

  通过由N -t-Boc-β-内酰胺4衍生的肟基6和甲酰恶唑啉13，已经开发出具有高对映体纯度的二肽等排体（例如，羟乙烯，二羟乙烯和羟乙胺等排体）的新型有效合成途径。
• Stereocontrolled synthesis of pseudo C2-symmetric 1,3-diamino-2-propanol core units of HIV protease inhibitors
  作者：Alessandro Dondoni、Daniela Perrone

  DOI：10.1016/s0040-4039(96)02355-6

  日期：1997.1

  The synthesis of the pseudo C2-symmetric dibenzyldiamino alcohol (S,S)-1 and the two meso stereoisomers 1a and 1b (R = PhCH2) is described by stereocontrolled benzylmagnesium chloride addition to the nitrones 3 derived from chiral β-amino-α-hydroxy aldehydes 2 that in turn were obtained from phenylalanine; the overall yield of (S,S)-1 is 23% from N-Boc l-phenylalaninal; the antipode (R,R)-1 can be

  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 。
• Aminediols for the treatment of Alzheimer's disease
  申请人：——

  公开号：US20040019086A1

  公开（公告）日：2004-01-29

  The present invention relates to compounds of formula (I): 1 useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

  本发明涉及式（I）化合物： 1 用于治疗阿尔茨海默病和其他类似疾病。这些化合物包括β-分泌酶的抑制剂，可用于治疗阿尔茨海默病和其他以哺乳动物体内Aβ肽沉积为特征的疾病。本发明的化合物可用于药物组合物和治疗方法，以减少 A beta 肽的形成。
• Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity
  作者：Suvit Thaisrivongs、Alfredo G. Tomasselli、Joseph B. Moon、John Hui、Thomas J. McQuade、Steve R. Turner、Joseph W. Strohbach、W. Jeffrey Howe、W. Gary Tarpley、Robert L. Heinrikson

  DOI：10.1021/jm00112a005

  日期：1991.8

  The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a K(i) of < 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.
• Grignard Addition to Aldonitrones. Stereochemical Aspects and Application to the Synthesis of C₂-Symmetric Diamino Alcohols and Diamino Diols
  作者：Alessandro Dondoni、Daniela Perrone、Marilisa Rinaldi

  DOI：10.1021/jo980980u

  日期：1998.12.1

  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.