(1S,2S)-2-[(tert-butyldiphenylsiloxy)methyl]-1-[2-((S)-tert-butylsulfinyl)iminoethyl]cyclopropane | 1046470-56-7

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (1S,2S)-2-[(tert-butyldiphenylsiloxy)methyl]-1-[2-((S)-tert-butylsulfinyl)iminoethyl]cyclopropane
• CAS: 1046470-56-7
• 化学式: C₂₆H₃₇NO₂SSi
• 分子量: 455.737
• InChiKey: GGLCIHGRIXFDFJ-WOGZVKCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.12
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.66
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (1S,2S)-2-[(tert-butyldiphenylsiloxy)methyl]-1-[2-((S)-tert-butylsulfinyl)iminoethyl]cyclopropane 在 盐酸 、 甲醇 、 sodium chlorite 、 2-甲基-2-丁烯 、 sodium dihydrogen phosphate dihydrate 、 叠氮磷酸二苯酯 、 sodium carbonate 、 potassium carbonate 、 戴斯-马丁氧化剂 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 、 叔丁醇 为溶剂， 反应 117.67h， 生成 benzyl N-[(2S)-1-[[(2R)-1-[(1S,2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropyl]-5-phenylpentan-2-yl]amino]-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  Potent Proteasome Inhibitors Derived from the Unnatural cis-Cyclopropane Isomer of Belactosin A: Synthesis, Biological Activity, and Mode of Action

  摘要：

  The natural product belactosin A (1) with a trans-cyclopropane structure is a useful prototype compound for developing potent proteasome (core particle, CP) inhibitors. To date, 1 and its analogues are the only CP ligands that bind to both the nonprimed S1 pocket as well as the primed substrate binding channel; however, these molecules harbor a high IC50 value of more than 1 mu M. We have performed structure activity relationship studies, thereby elucidating unnatural cis-cyclopropane derivatives of 1 that exhibit high potency to primarily block the chymotrypsin-like active site of the human constitutive (cCP) and immunoproteasome (iCP). The most active compound 3e reversibly inhibits cCP and iCP similarly with an IC50 of 5.7 nM. X-ray crystallographic analysis of the yeast proteasome in complex with 3e revealed that the ligand is accommodated predominantly into the primed substrate binding channel and covalently binds to the active site threonine residue via its beta-lactone ring-opening.

  DOI：

  10.1021/jm4002296
• 作为产物：
  描述：

  2-((1S,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)acetaldehyde 、 S-叔丁基亚磺酰胺 在 copper(II) sulfate 作用下， 以 二氯甲烷 为溶剂， 以98%的产率得到(1S,2S)-2-[(tert-butyldiphenylsiloxy)methyl]-1-[2-((S)-tert-butylsulfinyl)iminoethyl]cyclopropane
  参考文献：
  名称：

  Synthesis of 2,3- and 3,4-Methanoamino Acid Equivalents with Stereochemical Diversity and Their Conversion into the Tripeptide Proteasome Inhibitor Belactosin A and Its Highly Potent Cis-Cyclopropane Stereoisomer

  摘要：

  A series of chiral 2,3- and 3,4-methanoamino acid equivalents of stereochernical diversity were designed and synthesized from our chiral cyclopropane units, using a diastereoselective Grignard addition with (R)- or (S)-t-butanesulfinyl imines as the key step. These equivalents were converted into the proteasome inhibitor belactosin A and its cis-cyclopropane stereoisomer. The unnatural cis-isomer was shown to be more than twice as potent as belactosin A as a proteasome inhibitor.

  DOI：

  10.1021/ol8013304