L-N-(benzyloxycarbonyl)-O-<(1,1-dimethylethyl)dimethylsilyloxy>tyrosine methyl ester | 226211-52-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: L-N-(benzyloxycarbonyl)-O-<(1,1-dimethylethyl)dimethylsilyloxy>tyrosine methyl ester
• CAS: 226211-52-5
• 化学式: C₂₄H₃₃NO₅Si
• 分子量: 443.615
• InChiKey: CFCRFLSUSBXAOQ-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  73.86
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  L-N-(benzyloxycarbonyl)-O-<(1,1-dimethylethyl)dimethylsilyloxy>tyrosine methyl ester 在 咪唑 、 5%-palladium/activated carbon 、 氢气 、 二异丁基氢化铝 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.17h， 生成 (S)-imidazole-1-carboxylic acid (1-(p-(tert-butyldimethylsilyloxy)benzyl)-2,2-dimethoxyethyl)amide
  参考文献：
  名称：

  Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease

  摘要：

  Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media. Seven variants were prepared and tested in cellulo with our HIV-1 fusion-protein technology that result in an eGFP-based fluorescent readout. Three candidates showed inhibition potency above 20 mu M and toxicity at higher concentrations, making them attractive targets for further refinement. Importantly, our class of original inhibitor candidates is not recognized by two major multidrug resistance pumps, quite in contrast to most clinically applied HIV-1 protease inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.018
• 作为产物：
  描述：

  N-苄氧羰基-L-酪氨酸 在 咪唑 、 硫酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 L-N-(benzyloxycarbonyl)-O-<(1,1-dimethylethyl)dimethylsilyloxy>tyrosine methyl ester
  参考文献：
  名称：

  Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease

  摘要：

  Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media. Seven variants were prepared and tested in cellulo with our HIV-1 fusion-protein technology that result in an eGFP-based fluorescent readout. Three candidates showed inhibition potency above 20 mu M and toxicity at higher concentrations, making them attractive targets for further refinement. Importantly, our class of original inhibitor candidates is not recognized by two major multidrug resistance pumps, quite in contrast to most clinically applied HIV-1 protease inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.018

文献信息

• The total synthesis of the diepoxycyclohexanone antibiotic aranorosin and novel synthetic analogues
  作者：Alexander McKillop、Lee McLaren、Richard J. K. Taylor、Robert J. Watson、Norman J. Lewis

  DOI：10.1039/p19960001385

  日期：——

  A short synthesis of the novel antibiotic aranorosin in chiral form is described which employs (i) a novel hypervalent iodine-mediated oxidative hydroxylation of a tyrosinal derivative and (ii) a stereocontrolled cis-bisepoxidation in the key steps. A similar procedure was employed to prepare 6′-epiaranorosin, and hence establish the stereochemistry of the natural compound, and to prepare novel aranorosin

  描述了手性形式的新型抗生素阿糖胞苷的简短合成，其在关键步骤中采用了（i）酪氨酸衍生物的新型高价碘介导的氧化羟基化作用和（ii）立体控制的顺式-双环氧化。采用相似的方法制备6'-表皮阿糖胞苷，从而建立天然化合物的立体化学，并制备新的阿糖胞苷类似物。描述了一种有机金属路线，该路线产生了脱酰胺基芳族松香。
• Synthesis of a Series of Stromelysin-Selective Thiadiazole Urea Matrix Metalloproteinase Inhibitors
  作者：E. Jon Jacobsen、Mark A. Mitchell、Susan K. Hendges、Kenneth L. Belonga、Louis L. Skaletzky、Lindsay S. Stelzer、Thomas. J. Lindberg、Edward L. Fritzen、Heinrich J. Schostarez、Theresa J. O'Sullivan、Linda L. Maggiora、Christopher W. Stuchly、Alice L. Laborde、Marc F. Kubicek、Roger A. Poorman、Joan M. Beck、Henry R. Miller、Gary L. Petzold、Pam S. Scott、Scott E. Truesdell、Tanya L. Wallace、John W. Wilks、Christopher Fisher、Linda V. Goodman、Paul S. Kaytes、Stephen R. Ledbetter、Elaine A. Powers、Gabriel Vogeli、John E. Mott、Catherine M. Trepod、Douglas J. Staples、Eric T. Baldwin、Barry C. Finzel

  DOI：10.1021/jm9803222

  日期：1999.5.1

  The synthesis and enzyme inhibition data for a series of thiadiazole urea matrix metalloproteinase (MMP) inhibitors are described. A broad screening effort was utilized to identify several thiadiazoles which were weak inhibitors of stromelysin. Optimization of the thiadiazole leads to include an alpha-amino acid side chain with variable terminal amide substituents provided a series of ureas which were moderately effective stromelysin inhibitors, with K-i's between 0.3 and 1.0 mu M. The most effective analogues utilized an L-phenylalanine as the amino acid component. In particular, unsubstituted 46 had a K-i of 710 nM, while the p-fluoro analogue 52 displayed increased potency (100 nM). Stromelysin inhibition was further improved using a pentafluorophenylalanine substituent which resulted in 70, a 14 nM inhibitor. While gelatinase inhibition was generally poor, the use of 1-(2-pyridyl)piperazine as the amide component usually provided for enhanced activity, with 71 inhibiting gelatinase with a K-i of 770 nM. The combination of this heterocycle with a p-fluorophenylalanine substituent provided the only analogue, 69, with collagenase activity (13 mu M). The SAR for analogues described within this series can be rationalized through consideration of the X-ray structure recently attained for 70 complexed to stromelysin. Uniquely, this structure showed the inhibitor to be completely orientated on the left side of the enzyme cleft. These results suggest that thiadiazole urea heterocycles which incorporate a substituted phenylalanine can provide selective inhibitors of stromelysin. Careful selection of the amide substituent can also provide for analogues with modest gelatinase inhibition.