(2R,5R)-5-allyl-2-tert-butyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one | 81286-83-1

• 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: (2R,5R)-5-allyl-2-tert-butyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one
• 英文别名: (3R,7aR)-3-tert-butyl-7a-prop-2-enyl-3,5,6,7-tetrahydropyrrolo[1,2-c][1,3]oxazol-1-one
• CAS: 81286-83-1
• 化学式: C₁₃H₂₁NO₂
• 分子量: 223.315
• InChiKey: NUXPNXIZIUPGOM-MFKMUULPSA-N

物化性质

• 沸点：
  82-87 °C(Press: 0.01 Torr)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,5R)-5-allyl-2-tert-butyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one 在 sodium hydroxide 、 sodium tetrahydroborate 、 正丁基锂 、 二甲基硫 、 potassium carbonate 、 臭氧 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 邻二氯苯 为溶剂， 反应 16.33h， 生成 (-)-6-(R)-<(2E)-4-<(tert-butyldimethylsilyl)oxy>3-methylbut-2-enyl>-2,5-diketo-4-(4-methoxybenzyl)-1,4-diazabicyclo<4.3.0>nonane
  参考文献：
  名称：

  Williams, Robert M.; Glinka, Tomasz; Kwast, Ewa, Journal of the American Chemical Society, 1990, vol. 112, # 2, p. 808 - 821

  摘要：

  DOI：
• 作为产物：
  描述：

  L-脯氨酸 在 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 生成 (2R,5R)-5-allyl-2-tert-butyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one
  参考文献：
  名称：

  Design, Synthesis, and Dopamine Receptor Modulating Activity of Spiro Bicyclic Peptidomimetics of l-Prolyl-l-leucyl-glycinamide

  摘要：

  In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the ability of these systems to mimic the type-II beta-turn and (2) the effect that these structural perturbations would have on the ability of the peptidomimetics to modulate dopamine receptors. Through the use of the [H-3]spiroperidol/N-propylnorapomorphine (NPA) dopamine D-2 receptor competitive binding assay, 3 and 4, at a concentration of 100 nM, decreased the dissociation constant of the high-affinity state of the dopamine receptor for the agonist. These effects were observed when either Gpp(NH)p was absent or present and they were comparable to those produced by PLG at a concentration of 1 mu M. Peptidomimetics 3 and 4 also increased the percentage of D-2 receptors that existed in the high-affinity state. Even with Gpp(NH)p present, 3 and 4 were able to return the R-H/R-L ratios to values observed in the respective controls where Gpp(NH)p was absent. Furthermore, both peptidomimetics were able to attenuate the Gpp(NH)p-induced shift to the low-affinity state to a greater extent than PLG. Peptidomimetics 3 and 4 were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism, and each affected the rotational behavior in a bell-shaped dose-response relationship producing increases of 95 +/- 31% (0.01 mg/kg, ip) and 88 +/- 14% (0.001 mg/kg, ip), respectively. In comparison, the previously reported 5.5.5. spiro bicyclic lactam 2 increased rotational behavior by 25 +/- 11% (0.01 mg/kg, ip).

  DOI：

  10.1021/jm980525q

文献信息

• Facial selectivity of the intramolecular SN2' cyclization: stereocontrolled total synthesis of brevianamide B
  作者：Robert M. Williams、Tomasz. Glinka、Ewa. Kwast

  DOI：10.1021/ja00225a069

  日期：1988.8

  Synthese du compose du titre a partir d'allyl-7a t-butyl-3 perhydro pyrrolo [1,2-c] oxazolone-1

  Synthese du compose du titre a partir d'allyl-7a t-butyl-3 perhydro pyrrolo [1,2-c] oxazolone-1
• Alkylation of amino acids without loss of the optical activity: preparation of .alpha.-substituted proline derivatives. A case of self-reproduction of chirality
  作者：Dieter Seebach、Michael Boes、Reto Naef、W. Bernd Schweizer

  DOI：10.1021/ja00354a034

  日期：1983.8

  Preparation d'un enolate par condensation de proline avec le pivalaldehyde suivie de deprotonation. Etude des reactions de cet enolate avec divers electrophiles. Condensation du pivalaldehyde avec d'autres aminoacides

  制备 d'un enolate par 缩合脱脯氨酸 avec le 新戊醛 suvie de 质子化。Etude des反应 de cet enolate avec divers 亲电试剂。新戊醛缩合氨基酸
• Synthesis, conformational properties, and antibody recognition of peptides containing .beta.-turn mimetics based on .alpha.-alkylproline derivatives
  作者：Mark G. Hinds、John H. Welsh、David M. Brennand、J. Fisher、Martin J. Glennie、Nigel G. J. Richards、David L. Turner、John A. Robinson

  DOI：10.1021/jm00110a005

  日期：1991.6

  Peptide recognition by monoclonal antibodies may provide a useful model for drug development, in particular to test the effects of conformational restriction on ligand binding. We have tested the influence of novel peptide mimetics upon conformation and binding affinity for the case of monoclonal antibodies raised to a peptide antigen which displays a preference for a beta-turn conformation in aqueous solution. Two monoclonals were isolated that recognized the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala specifically at the beta-turn formed by Tyr-Pro-Tyr-Asp. Peptide analogues were then synthesized containing mimetics designed to stabilize this conformation. One, analogue (3), contained a spirocyclic gamma-lactam bridge between the alpha-position of proline-2 and the N atom of tyrosine-3, while another (2) contained (S)-alpha-methylproline at position 2. NMR spectroscopy and molecular modeling suggest that both analogues adopt reverse-turn conformations stabilized relative to that in the native sequence. For the (S)-alpha-methylproline analogue binding to both monoclonal antibodies was substantially improved, compared with the native antigen, whereas the gamma-lactam analogue (3) was not recognized by either antibody. Quantitative equilibrium ultrafiltration binding assays showed that the affinities of the (S)-alpha-methylproline analogue (2) for the two antibodies were improved over those measured with the native antigen by -2.3 and -0.65 kcal/mol. The origins of these free energy differences cannot be explained wholly on the basis of presumed extra hydrophobic contacts between the new methyl substituent and the antigen binding sites. We propose that the increased conformational stability of the analogue plays a decisive role, implying that the reverse turn detected in the native antigen, possibly a type-I turn, is important for recognition by the two antibodies.
• Design, Synthesis, and In Vitro Activity of Peptidomimetic Inhibitors of Myeloid Differentiation Factor 88
  作者：Nicola Fantò、Grazia Gallo、Andrea Ciacci、Mauro Semproni、Davide Vignola、Marco Quaglia、Valentina Bombardi、Domenico Mastroianni、M. Pia Zibella、Giancarlo Basile、Marica Sassano、Vito Ruggiero、Rita De Santis、Paolo Carminati

  DOI：10.1021/jm070723u

  日期：2008.3.13

  We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH(2), belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The ability of the peptidomimetics to inhibit protein-protein interaction was assessed by yeast 2-hybrid assay and further validated in a mammalian cell system by evaluating the inhibition of NF-kappa B activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.
• Synthesis of an Optically Active 1-Azaspiro[4.4]non-8-en-7-one
  作者：Masazumi Ikeda、Masazumi Ikeda、Ken-ichiro Matsubayashi、Takayuki Imoto、Kaoru Kitao、Hiroyuki Ishibashi、Tatsunori Sato

  DOI：10.3987/com-94-6734

  日期：——

  The 1-azaspiro[4.4]non-8-en-7-one (7) and its (R)-9-(3,4-methylenedioxyphenyl)-substituted derivative (12) have been synthesized using an intramolecular aldol condensation of the pyrrolidine derivatives (6) and (11) as a key step.