tert-butyl ((2S,6S)-6-ethyl-5-oxo-5,6-dihydro-2H-pyran-2-yl) carbonate | 1268341-13-4

• 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)-6-ethyl-5-oxo-5,6-dihydro-2H-pyran-2-yl) carbonate
• CAS: 1268341-13-4
• 化学式: C₁₂H₁₈O₅
• 分子量: 242.272
• InChiKey: OJULXEUDIREZPQ-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 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)-6-ethyl-5-oxo-5,6-dihydro-2H-pyran-2-yl) carbonate 在 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 15.0h， 生成 5,7-bis(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-(((2S,3R,4R,5R,6S)-6-ethyl-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-4H-chromen-4-one
  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：

  2-丙酰呋喃 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 (1S,2S)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine-ruthenium(mesitylene) 、 sodium formate 、 sodium acetate 、 十六烷基三甲基溴化铵 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 37.0h， 生成 、 tert-butyl ((2S,6S)-6-ethyl-5-oxo-5,6-dihydro-2H-pyran-2-yl) carbonate
  参考文献：
  名称：

  C5′-Alkyl Substitution Effects on Digitoxigenin α-l-Glycoside Cancer Cytotoxicity

  摘要：

  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.

  DOI：

  10.1021/ml100291n