tert-butyl ((2S,6S)-5-oxo-6-propyl-5,6-dihydro-2H-pyran-2-yl) carbonate | 1268341-14-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: tert-butyl ((2S,6S)-5-oxo-6-propyl-5,6-dihydro-2H-pyran-2-yl) carbonate
• CAS: 1268341-14-5
• 化学式: C₁₃H₂₀O₅
• 分子量: 256.299
• InChiKey: IRWBOXMLZNMDPU-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.59
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl ((2S,6S)-5-oxo-6-propyl-5,6-dihydro-2H-pyran-2-yl) carbonate 在 吡啶 、 4-二甲氨基吡啶 、 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 sodium tetrahydroborate 、 四氧化锇 、 cerium(III) chloride 、 N-甲基吗啉氧化物 、 三苯基膦 、 叔丁醇 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 32.0h， 生成 (2S,3R,4S,5R,6S)-6-((5,7-bis(benzyloxy)-2-(4-(benzyloxy)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-4,5-dihydroxy-2-propyltetrahydro-2H-pyran-3-yl acetate
  参考文献：
  名称：

  Improving the Affinity of SL0101 for RSK Using Structure-Based Design

  摘要：

  Enhanced activity of the Ser/Thr protein kinase, RSK, is associated with transformation and metastasis, which suggests that RSK is an attractive drug target. The natural product SL0101 (kaempferol 3-O-(3 '',4 ''-di-O-acetyl-alpha-L-rhamnopyranoside)) has been shown to be an RSK selective inhibitor. However, the K-i for SL0101 is 1 mu M with a half-life of less than 30 min in vivo. To identify analogues with improved efficacy we designed a set of analogues based on the crystallographic model of SL0101 in complex with the RSK2 N-terminal kinase domain. We identified an analogue with a 5 ''-n-propyl group on the rhamnose that has >40-fold improved affinity for RSK relative to SL0101 in an in vitro kinase assay. This analogue preferentially inhibited the proliferation of the human breast cancer line, MCF-7, versus the normal untransformed breast line, MCF-10A, which is consistent with results using SL0101. However, the efficacy of the 5 ''-n-propyl analogue to inhibit MCF-7 proliferation was only 2-fold better than for SL0101, which we hypothesize is due to limited membrane permeability. The improved affinity of the 5 ''-n-propyl analogue for RSK will aid in the design of future compounds for in vivo use.

  DOI：

  10.1021/ml300298v
• 作为产物：
  描述：

  1-(2-furyl)-1-butanol 在 sodium acetate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成 tert-butyl ((2S,6S)-5-oxo-6-propyl-5,6-dihydro-2H-pyran-2-yl) carbonate
  参考文献：
  名称：

  烯丙基-烯丙基偶联对钯催化的区域选择性和非对映选择性C-糖基化

  摘要：

  在温和条件下，使用Achmatowicz重排产物作为供体，甲基香豆素作为受体，通过烯丙基-烯丙基偶联过程开发了Pd催化的C-糖基化反应。该方法具有区域选择性和非对映选择性，C-糖苷的立体发散合成。具有控制的立体多样性的糖基供体和具有荧光性能的糖基受体进一步强调了该方法。

  DOI：

  10.1002/adsc.202001136

文献信息

• De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101
  作者：Roman M. Mrozowski、Zachary M. Sandusky、Rajender Vemula、Bulan Wu、Qi Zhang、Deborah A. Lannigan、George A. O’Doherty

  DOI：10.1021/ol503012k

  日期：2014.11.21

  SL0101, C4″-amide/C6″-alkyl substituted analogues of SL0101 were synthesized and evaluated in cell-based assays. The analogues were prepared using a de novo asymmetric synthetic approach, which featured Pd-π-allylic catalyzed glycosylation for the introduction of a C4″-azido group. Surprisingly replacement of the C4″-acetate with a C4″-amide resulted in analogues that were no longer specific for RSK in

  为了改善已知的核糖体 s6 激酶 (RSK) 抑制剂 SL0101 的体内半衰期，合成了 SL0101 的 C4"-酰胺/C6"-烷基取代类似物，并在基于细胞的测定中进行了评估。类似物是使用从头不对称合成方法制备的，其特征是 Pd-π-烯丙基催化糖基化以引入 C4"-叠氮基。令人惊讶的是，用 C4"-酰胺替代 C4"-乙酸酯导致在基于细胞的测定中不再对 RSK 具有特异性的类似物。
• C5′-Alkyl Substitution Effects on Digitoxigenin α-<scp>l</scp>-Glycoside Cancer Cytotoxicity
  作者：Hua-Yu Leo Wang、Bulan Wu、Qi Zhang、Sang-Woo Kang、Yon Rojanasakul、George A. O’Doherty

  DOI：10.1021/ml100291n

  日期：2011.4.14

  A highly regio- and stereoselective asymmetric synthesis of various CS'-alkyl side chains of rhamnosyl- and amicetosyl-digitoxigenin analogues has been established via palladium-catalyzed glycosylation with postglycosylated dihydroxylation or diimide reduction. The C5'-methyl group in both alpha-L-rhamnose and cc-L-amicetose digitoxin analogues displayed a steric directed apoptosis induction and tumor growth inhibition against nonsmall cell human lung cancer cells (NCI-H460). The antitumor activity is significantly reduced when the steric hindrance is increased at the C5'-stereocenter.