(1S,4R,7R,10R,13S,16S)-7-(hydroxymethyl)-24-methoxy-10-[(4-methoxyphenyl)methyl]-4,9,13,15,29-pentamethyl-22-oxa-3,6,9,12,15,29-hexazatetracyclo[14.12.2.218,21.123,27]tritriaconta-18,20,23,25,27(31),32-hexaene-2,5,8,11,14,30-hexone | 70840-66-3

• 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: (1S,4R,7R,10R,13S,16S)-7-(hydroxymethyl)-24-methoxy-10-[(4-methoxyphenyl)methyl]-4,9,13,15,29-pentamethyl-22-oxa-3,6,9,12,15,29-hexazatetracyclo[14.12.2.218,21.123,27]tritriaconta-18,20,23,25,27(31),32-hexaene-2,5,8,11,14,30-hexone
• CAS: 70840-66-3；138923-14-5
• 化学式: C₄₁H₅₀N₆O₁₀
• 分子量: 786.882
• InChiKey: WASXNYRXXQONPG-LDJAUVLGSA-N

物化性质

• 沸点：
  1116.3±65.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  57
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  196
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (1S,4R,7R,10R,13S,16S)-7-(hydroxymethyl)-24-methoxy-10-[(4-methoxyphenyl)methyl]-4,9,13,15,29-pentamethyl-22-oxa-3,6,9,12,15,29-hexazatetracyclo[14.12.2.218,21.123,27]tritriaconta-18,20,23,25,27(31),32-hexaene-2,5,8,11,14,30-hexone 、 碘甲烷 在 aluminum oxide 、 potassium fluoride 作用下， 以 乙二醇二甲醚 为溶剂， 反应 24.0h， 以100%的产率得到
  参考文献：
  名称：

  New antitumor bicyclic hexapeptides, RA-VI and -VIII from rubia cordifolia ; Conformation-activity relationship II

  摘要：

  The structures of new antitumor bicyclic hexapeptides, RA-VI and -VIII from Rubia cordifolia were elucidated by the spectroscopic and chemical methods. A combination of two-dimentional NMR techniques and NOE relationships showed that the amino acids constituting the beta-turn of RA-VI are Ser-2 and D-Tyr-3 and those of RA-VIII, Thr-2 and Tyr-3. By the conformational analysis of RA-VI in its crystalline state using the X-ray diffractometric technique, RA-VI was shown to have, in its solid state, a type V beta-turn structure at the residues Ser-2 and D-Tyr-3, while other RAs have type II beta-turns. Further, by 2D-NMR techniques, temperature effects on NH protons and NOE experiments, in solution of CDCl3, RA-VI was shown to exist only as conformer A and RA-VIII as conformers A, B and C. The difference between the solid state and solution state conformations of RA-VI was also shown by the refinement of the restrained molecular dynamics calculations using AMBER program. RA-VIII, having a smaller population of conformer A with type II beta-turn than other RAs, showed a reduced biological activity, and the N-methyl derivative of RA-VIII, whose conformer A content is further reduced, gave a further reduced activity, suggesting that conformer A contributes to the activity. However, RA-VI, existing in solution 100% as conformer A, showed a very low activity and N-methylation increased the activity. This shows that the stereochemistry and molecular mobility of the aromatic side chain of Tyr-3 over this turn, as elucidated by the C-13 spin lattice relaxation times, plays a more important role in the antitumor activity of the compounds of this series in addition to the type II beta-turn structures.

  DOI：

  10.1016/s0040-4020(01)96155-1

文献信息

• New antitumor bicyclic hexapeptides, RA-VI and -VIII from rubia cordifolia ; Conformation-activity relationship II
  作者：Hideji Itokawa、Hiroshi Morita、Koichi Takeya、Nobuo Tomioka、Akiko Itai、Yoichi Iitaka

  DOI：10.1016/s0040-4020(01)96155-1

  日期：1991.8

  The structures of new antitumor bicyclic hexapeptides, RA-VI and -VIII from Rubia cordifolia were elucidated by the spectroscopic and chemical methods. A combination of two-dimentional NMR techniques and NOE relationships showed that the amino acids constituting the beta-turn of RA-VI are Ser-2 and D-Tyr-3 and those of RA-VIII, Thr-2 and Tyr-3. By the conformational analysis of RA-VI in its crystalline state using the X-ray diffractometric technique, RA-VI was shown to have, in its solid state, a type V beta-turn structure at the residues Ser-2 and D-Tyr-3, while other RAs have type II beta-turns. Further, by 2D-NMR techniques, temperature effects on NH protons and NOE experiments, in solution of CDCl3, RA-VI was shown to exist only as conformer A and RA-VIII as conformers A, B and C. The difference between the solid state and solution state conformations of RA-VI was also shown by the refinement of the restrained molecular dynamics calculations using AMBER program. RA-VIII, having a smaller population of conformer A with type II beta-turn than other RAs, showed a reduced biological activity, and the N-methyl derivative of RA-VIII, whose conformer A content is further reduced, gave a further reduced activity, suggesting that conformer A contributes to the activity. However, RA-VI, existing in solution 100% as conformer A, showed a very low activity and N-methylation increased the activity. This shows that the stereochemistry and molecular mobility of the aromatic side chain of Tyr-3 over this turn, as elucidated by the C-13 spin lattice relaxation times, plays a more important role in the antitumor activity of the compounds of this series in addition to the type II beta-turn structures.