Benzyl-carbamic acid (2R,5S,8S,9R,13R,13aS)-9-heptyl-5-isopropyl-13-(4-methoxy-benzyloxy)-8-methyl-4,7,11-trioxo-decahydro-6,10-dioxa-3a-aza-cyclopentacyclododecen-2-yl ester | 187479-03-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: Benzyl-carbamic acid (2R,5S,8S,9R,13R,13aS)-9-heptyl-5-isopropyl-13-(4-methoxy-benzyloxy)-8-methyl-4,7,11-trioxo-decahydro-6,10-dioxa-3a-aza-cyclopentacyclododecen-2-yl ester
• 英文别名: [(3S,6S,7R,11R,12S,14R)-7-heptyl-11-[(4-methoxyphenyl)methoxy]-6-methyl-2,5,9-trioxo-3-propan-2-yl-4,8-dioxa-1-azabicyclo[10.3.0]pentadecan-14-yl] N-benzylcarbamate
• CAS: 187479-03-4
• 化学式: C₃₉H₅₄N₂O₉
• 分子量: 694.866
• InChiKey: QSOAQQICAPRMSL-MVSKMXPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  50
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Benzyl-carbamic acid (2R,5S,8S,9R,13R,13aS)-9-heptyl-5-isopropyl-13-(4-methoxy-benzyloxy)-8-methyl-4,7,11-trioxo-decahydro-6,10-dioxa-3a-aza-cyclopentacyclododecen-2-yl ester 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.5h， 以71%的产率得到[(3S,6S,7R,11R,12S,14R)-7-heptyl-11-hydroxy-6-methyl-2,5,9-trioxo-3-propan-2-yl-4,8-dioxa-1-azabicyclo[10.3.0]pentadecan-14-yl] N-benzylcarbamate
  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：

  L-羟基脯氨酸 在 W-2 Raney Ni 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 三氟甲磺酸 、 氢氟酸 、 氢气 、 双氧水 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 二异丁基氢化铝 、 sodium carbonate 、 臭氧 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， -78.0~85.0 ℃ 、101.33 kPa 条件下， 生成 Benzyl-carbamic acid (2R,5S,8S,9R,13R,13aS)-9-heptyl-5-isopropyl-13-(4-methoxy-benzyloxy)-8-methyl-4,7,11-trioxo-decahydro-6,10-dioxa-3a-aza-cyclopentacyclododecen-2-yl ester
  参考文献：
  名称：

  Analogs Incorporating trans-4-Hydroxy-l-proline That Reverse Multidrug Resistance Better Than Hapalosin

  摘要：

  DOI：

  10.1021/jo962180u

文献信息

• Synthesis, Conformational Analysis, and Evaluation of the Multidrug Resistance-Reversing Activity of the Triamide and Proline Analogs of Hapalosin
  作者：Tam Q. Dinh、Xiaohui Du、Charles D. Smith、Robert W. Armstrong

  DOI：10.1021/jo9708396

  日期：1997.10.1

  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.
• Analogs Incorporating <i>trans</i>-4-Hydroxy-<scp>l</scp>-proline That Reverse Multidrug Resistance Better Than Hapalosin
  作者：Tam Q. Dinh、Charles D. Smith、Robert W. Armstrong

  DOI：10.1021/jo962180u

  日期：1997.2.1