(S)-4-(9H-Fluoren-9-ylmethoxycarbonylmethyl)-5-oxo-oxazolidine-3-carboxylic acid benzyl ester | 122235-68-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-4-(9H-Fluoren-9-ylmethoxycarbonylmethyl)-5-oxo-oxazolidine-3-carboxylic acid benzyl ester
• 英文别名: benzyl (4S)-4-[2-(9H-fluoren-9-ylmethoxy)-2-oxoethyl]-5-oxo-1,3-oxazolidine-3-carboxylate
• CAS: 122235-68-1
• 化学式: C₂₇H₂₃NO₆
• 分子量: 457.483
• InChiKey: YPZSVZKKJWWAFJ-DEOSSOPVSA-N

物化性质

• 熔点：
  128-130 °C
• 沸点：
  664.5±55.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.25
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.14
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-4-(9H-Fluoren-9-ylmethoxycarbonylmethyl)-5-oxo-oxazolidine-3-carboxylic acid benzyl ester 在 盐酸 、 氢溴酸 、 溶剂黄146 作用下， 生成 L-aspartic acid γ-fluorenylmethyl ester hydrochloride
  参考文献：
  名称：

  Potent and prolonged-acting cyclic lactam analogs of .alpha.-melanotropin: design based on molecular dynamics

  摘要：

  Utilizing results from previous structure-activity relationships and theoretical studies of alpha-melanotropin (alpha-MSH, Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and its related superpotent analogues, Ac-[Nle4,D-Phe7]-alpha-MSH and Ac-[Cys4,Cys10]-alpha-MSH, we have designed a new class of alpha-MSH4-13 and alpha-MSH4-10 cyclic lactam fragment analogues of alpha-melanotropin. The cyclic peptides have the following general structures: Ac-[Nle4,Xxx5,D-Phe7,Yyy10,Gly11]-alpha-MSH4-13- NH2 and Ac-[Nle4,Xxx5,D-Phe7,Yyy10]-alpha-MSH4-10-NH2, where Xxx = Glu or Asp and Yyy = Lys, Orn, Dab, or Dpr. Formation of the lactam bridge between the side-chain groups Xxx and Yyy was performed either in solution or on a solid-phase support. Seven cyclic peptides were prepared and bioassayed for their melanotropic potency by using standard frog (Rana pipiens) and lizard (Anolis carolinensis) skin bioassays. Relative to alpha-MSH (relative potency = 1), the potencies of the cyclic peptides in the lizard skin bioassay were as follows: alpha-MSH (1); Ac-[Nle4,Glu5,D-Phe7,Lys10,Gly11]-alpha-MSH4-13- NH2 (6); Ac-[Nle4,Asp5,D-Phe7,Lys10,Gly11]-alpha-MSH4-13- NH2 (100); Ac-[Nle4,Glu5,D-Phe7,Lys10]-alpha-MSH4-10-NH2 (9); Ac-[Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH4-10-NH2 (90); Ac-[Nle4,Asp5,D-Phe7,Orn10]-alpha-MSH4-10-NH2 (20); Ac-[Nle4,Asp5,D-Phe7,Dab10]-alpha-MSH4-10-NH2 (5); Ac-[Nle4,Asp5,D-Phe7,Dpr10]-alpha-MSH4-10-NH2 (5). Similar results were obtained in the frog skin bioassay, but the analogues were much less potent. Cyclic melanotropins with 23-membered rings exhibited 100-fold higher melanotropic potency than alpha-MSH with selectivity for the lizard melanocyte receptors over the frog melanocyte receptors. Increasing or decreasing the ring size of these cyclic melanotropins from 23 diminishes the biological potency of the resulting cyclic peptide. The 23- and 24-membered ring analogues showed prolonged (residual) biological activities in both biological assays, but the smaller ring systems (20, 21, 22) did not. These results provide new insights into the structural and conformational requirements of alpha-MSH and its analogues at two different types of pigment cell (melanocyte) receptors.

  DOI：

  10.1021/jm00132a010
• 作为产物：
  描述：

  9-芴甲醇 、 (S)-(+)-3(苄氧羰基)-5-氧代-4-恶唑啉乙酸 在 4-二甲氨基吡啶 、 1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide methiodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到(S)-4-(9H-Fluoren-9-ylmethoxycarbonylmethyl)-5-oxo-oxazolidine-3-carboxylic acid benzyl ester
  参考文献：
  名称：

  Potent and prolonged-acting cyclic lactam analogs of .alpha.-melanotropin: design based on molecular dynamics

  摘要：

  Utilizing results from previous structure-activity relationships and theoretical studies of alpha-melanotropin (alpha-MSH, Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and its related superpotent analogues, Ac-[Nle4,D-Phe7]-alpha-MSH and Ac-[Cys4,Cys10]-alpha-MSH, we have designed a new class of alpha-MSH4-13 and alpha-MSH4-10 cyclic lactam fragment analogues of alpha-melanotropin. The cyclic peptides have the following general structures: Ac-[Nle4,Xxx5,D-Phe7,Yyy10,Gly11]-alpha-MSH4-13- NH2 and Ac-[Nle4,Xxx5,D-Phe7,Yyy10]-alpha-MSH4-10-NH2, where Xxx = Glu or Asp and Yyy = Lys, Orn, Dab, or Dpr. Formation of the lactam bridge between the side-chain groups Xxx and Yyy was performed either in solution or on a solid-phase support. Seven cyclic peptides were prepared and bioassayed for their melanotropic potency by using standard frog (Rana pipiens) and lizard (Anolis carolinensis) skin bioassays. Relative to alpha-MSH (relative potency = 1), the potencies of the cyclic peptides in the lizard skin bioassay were as follows: alpha-MSH (1); Ac-[Nle4,Glu5,D-Phe7,Lys10,Gly11]-alpha-MSH4-13- NH2 (6); Ac-[Nle4,Asp5,D-Phe7,Lys10,Gly11]-alpha-MSH4-13- NH2 (100); Ac-[Nle4,Glu5,D-Phe7,Lys10]-alpha-MSH4-10-NH2 (9); Ac-[Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH4-10-NH2 (90); Ac-[Nle4,Asp5,D-Phe7,Orn10]-alpha-MSH4-10-NH2 (20); Ac-[Nle4,Asp5,D-Phe7,Dab10]-alpha-MSH4-10-NH2 (5); Ac-[Nle4,Asp5,D-Phe7,Dpr10]-alpha-MSH4-10-NH2 (5). Similar results were obtained in the frog skin bioassay, but the analogues were much less potent. Cyclic melanotropins with 23-membered rings exhibited 100-fold higher melanotropic potency than alpha-MSH with selectivity for the lizard melanocyte receptors over the frog melanocyte receptors. Increasing or decreasing the ring size of these cyclic melanotropins from 23 diminishes the biological potency of the resulting cyclic peptide. The 23- and 24-membered ring analogues showed prolonged (residual) biological activities in both biological assays, but the smaller ring systems (20, 21, 22) did not. These results provide new insights into the structural and conformational requirements of alpha-MSH and its analogues at two different types of pigment cell (melanocyte) receptors.

  DOI：

  10.1021/jm00132a010

文献信息

• AL-OBEIDI, FAHAD;CASTRUCCI, ANA M. DE L.;HADLEY, MAC E.;HRUBY, VICTOR J., J. MED. CHEM., 32,(1989) N2, C. 2555-2561
  作者：AL-OBEIDI, FAHAD、CASTRUCCI, ANA M. DE L.、HADLEY, MAC E.、HRUBY, VICTOR J.

  DOI：——

  日期：——
• AL-OBEIDI, FAHAD;SANDERSON, DOUGLAS G.;HRUBY, VICTOR J., INT. J. PEPTIDE AND PROTEIN RES., 35,(1990) N, C. 215-218
  作者：AL-OBEIDI, FAHAD、SANDERSON, DOUGLAS G.、HRUBY, VICTOR J.

  DOI：——

  日期：——