| 1046470-59-0

• 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
• CAS: 1046470-59-0
• 化学式: C₂₈H₄₁NO₂SSi
• 分子量: 483.791
• InChiKey: XCSOZXKNIRPBJQ-UDWIDTORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 、 sodium chlorite 、 2-甲基-2-丁烯 、 草酰氯 、 sodium dihydrogen phosphate dihydrate 、 叠氮磷酸二苯酯 、 四丁基氟化铵 、 三甲基乙酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 甲苯 、 叔丁醇 为溶剂， 反应 79.25h， 生成 tert-butyl N-[(2S)-1-[[(2S)-1-[(1S,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]but-3-en-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：

  (1S,2S)-2-[(tert-butyldiphenylsiloxy)methyl]-1-[2-((S)-tert-butylsulfinyl)iminoethyl]cyclopropane 、 乙烯基溴化镁 以 甲苯 为溶剂， 生成 、
  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

文献信息

• Three-dimensional structure-activity relationship study of belactosin A and its stereo- and regioisomers: development of potent proteasome inhibitors by a stereochemical diversity-oriented strategy
  作者：Keisuke Yoshida、Kazuya Yamaguchi、Akira Mizuno、Yuka Unno、Akira Asai、Takayuki Sone、Hideyoshi Yokosawa、Akira Matsuda、Mitsuhiro Arisawa、Satoshi Shuto

  DOI：10.1039/b900384c

  日期：——

  The development of potent proteasome inhibitors based on the stereochemical diversity-oriented strategy using a conformationally rigid cyclopropane structure was investigated. Thus, a series of stereo- and regioisomeric analogs of belactosin A (2), a cyclopropane amino acid (methanoamino acid)-containing tripeptidic proteasome inhibitor, were designed, in which the central cyclopropane amino acid part

  研究了基于构象刚性环丙烷结构的基于立体化学多样性导向策略的有效蛋白酶体抑制剂的开发。因此，设计了一系列的Belactosin A（2）立体异构体和区域异构体，这是一种含有环丙烷氨基酸（甲氨基氨基酸）的三肽蛋白酶体抑制剂，其中中央的环丙烷氨基酸部分被相应的立体异构体或区域异构体。使用一系列立体异构体的环丙烷氨基酸等效物，具有顺/反，D / L和syn / anti我们先前开发的立体化学多样性作为关键单元，已成功合成了目标化合物。生物学评价表明，如所预期，化合物活性改取决于中心环丙烷氨基酸部分的立体化学：在反式/ L-顺式异构体7和所述顺式/ L-抗-异构体9分别超过两倍强效天然Belactosin A（反式/ L-反异构体）。此外，三肽化合物13，非天然的顺式/ L-抗异构体9的合成前体被鉴定为高效蛋白酶体抑制剂。该化合物的效力是贝洛斯托因A的20倍，甚至比众所周知的抑制剂乳腺抑肽（4）更有