[(R)-1-((S)-1-{(S)-1-[((1S,2R)-1-Benzyl-2-hydroxy-pent-4-enyl)-methyl-carbamoyl]-2-methyl-propylcarbamoyl}-ethyl)-octyl]-carbamic acid benzyl ester | 196102-86-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(R)-1-((S)-1-{(S)-1-[((1S,2R)-1-Benzyl-2-hydroxy-pent-4-enyl)-methyl-carbamoyl]-2-methyl-propylcarbamoyl}-ethyl)-octyl]-carbamic acid benzyl ester
• 英文别名: benzyl N-[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-3-hydroxy-1-phenylhex-5-en-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-2-methyl-1-oxodecan-3-yl]carbamate
• CAS: 196102-86-0
• 化学式: C₃₇H₅₅N₃O₅
• 分子量: 621.861
• InChiKey: ABHUZRRTZIOVTI-JMMDVVQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  45
• 可旋转键数：
  21
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(R)-1-((S)-1-{(S)-1-[((1S,2R)-1-Benzyl-2-hydroxy-pent-4-enyl)-methyl-carbamoyl]-2-methyl-propylcarbamoyl}-ethyl)-octyl]-carbamic acid benzyl ester 在 palladium on activated charcoal 2,6-二甲基吡啶 、 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 臭氧 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 46.05h， 生成 (3S,6S,7R,11R,12S)-12-Benzyl-11-(tert-butyl-dimethyl-silanyloxy)-7-heptyl-3-isopropyl-1,6-dimethyl-1,4,8-triaza-cyclododecane-2,5,9-trione
  参考文献：
  名称：

  Synthesis, Conformational Analysis, and Evaluation of the Multidrug Resistance-Reversing Activity of the Triamide and Proline Analogs of Hapalosin

  摘要：

  Four analogs were synthesized which have trans-4-hydroxyl-L-proline replacing the N-Me-L-phenylalanine moiety in hapalosin. The triamide analog of hapalosin containing two secondary amide bonds in lieu of the two ester bonds in hapalosin was also synthesized. Conformations of hapalosin, the triamide analog, and two of the four proline analogs in chloroform were calculated utilizing distance constraints between NOESY-correlated protons. The lowest-energy, distance-constrained conformation of hapalosin is similar to that of the triamide analog and does not differ substantially from that of the two proline analogs. All conformations have an s-cis tertiary amide bond. The analogs' ability to reverse P-glycoprotein-mediated multidrug resistance was evaluated in cytotoxicity and drug accumulation assays using MCF-7/ADR cells which overexpress P-glycoprotein. Two of the proline analogs are more potent than hapalosin (which has a similar activity as verapamil) whereas the other two proline analogs and the triamide analog are less active than hapalosin.

  DOI：

  10.1021/jo9708396
• 作为产物：
  描述：

  [(R)-1-((S)-1-Methyl-2-oxo-ethyl)-octyl]-carbamic acid benzyl ester 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 30.0h， 生成 [(R)-1-((S)-1-{(S)-1-[((1S,2R)-1-Benzyl-2-hydroxy-pent-4-enyl)-methyl-carbamoyl]-2-methyl-propylcarbamoyl}-ethyl)-octyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Synthesis, Conformational Analysis, and Evaluation of the Multidrug Resistance-Reversing Activity of the Triamide and Proline Analogs of Hapalosin

  摘要：

  Four analogs were synthesized which have trans-4-hydroxyl-L-proline replacing the N-Me-L-phenylalanine moiety in hapalosin. The triamide analog of hapalosin containing two secondary amide bonds in lieu of the two ester bonds in hapalosin was also synthesized. Conformations of hapalosin, the triamide analog, and two of the four proline analogs in chloroform were calculated utilizing distance constraints between NOESY-correlated protons. The lowest-energy, distance-constrained conformation of hapalosin is similar to that of the triamide analog and does not differ substantially from that of the two proline analogs. All conformations have an s-cis tertiary amide bond. The analogs' ability to reverse P-glycoprotein-mediated multidrug resistance was evaluated in cytotoxicity and drug accumulation assays using MCF-7/ADR cells which overexpress P-glycoprotein. Two of the proline analogs are more potent than hapalosin (which has a similar activity as verapamil) whereas the other two proline analogs and the triamide analog are less active than hapalosin.

  DOI：

  10.1021/jo9708396