Boc-Ser-Ψ[(Z)CH=C]-Pro-OH | 345341-72-2

• 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: Boc-Ser-Ψ[(Z)CH=C]-Pro-OH
• 英文别名: (1R,2Z)-2-[(2R)-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propylidene]cyclopentane-1-carboxylic acid
• CAS: 345341-72-2
• 化学式: C₁₄H₂₃NO₅
• 分子量: 285.34
• InChiKey: RYPPAOUYZSKORV-ZNWQGHSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-Ser-Ψ[(Z)CH=C]-Pro-OH 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 (R)-2-[(R)-2-Amino-3-hydroxy-prop-(Z)-ylidene]-cyclopentanecarboxylic acid
  参考文献：
  名称：

  Conformationally Locked Isostere of PhosphoSer−cis-Pro Inhibits Pin1 23-Fold Better than PhosphoSer−trans-Pro Isostere

  摘要：

  Stereoisomeric cis and trans substrate analogues for Pint were designed and synthesized. The central phosphoSer-Pro core of the Pin1 substrate was replaced by cis and trans amide isosteres in Ac-Phe-Phe-pser-Psi[(Z and E)CH=C]-Pro-Arg-NH2, 1 and 2, peptidomimetics. They were synthesized on solid phase in 17% yield for the cis analogue 1, and 16% yield for the trans analogue 2. A second trans amide isostere with a C-terminal N-methylamide 3 was synthesized in 7% yield. The protease-coupled Pint assay showed that all three compounds inhibited the Pint peptidyl-prolyl isomerase (PPlase) enzymatic activity. The cis isostere 1 was 23 times more potent (K-i = 1.74 +/- 0.08 muM) than its trans counterpart 2 (K-i = 40 +/- 2 muM) in competitive inhibition of Pint. These results suggest that the catalytic site of Pin1 binds cis substrates more tightly in aqueous solution. Antiproliferative activity toward the A2780 human ovarian cancer cell line by the cis and trans analogues correlates with Pint inhibition results.

  DOI：

  10.1021/ja046396m
• 作为产物：
  描述：

  cyclopentanone hydrazone 在 palladium dihydroxide sodium tetrahydroborate 、 甲酸 、 jones reagent 、 cerium(III) chloride 、 18-冠醚-6 、 1,1,2,3-四甲基胍 、 碘 、 仲丁基锂 、 sodium 、 potassium hydride 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 环己烷 、 氨 、 丙酮 为溶剂， 反应 29.08h， 生成 Boc-Ser-Ψ[(Z)CH=C]-Pro-OH
  参考文献：
  名称：

  丝氨酸-顺-脯氨酸和丝氨酸-反-脯氨酸等排物：Still-Wittig和Ireland-Claisen重排的（Z）-和（E）-烯烃模拟物的立体选择性合成。

  摘要：

  设计并立体选择性合成了两个新的Ser-cis-Pro和Ser-trans-Pro酰胺同分异构体，以掺入磷酸化依赖性肽基脯氨酰异构酶Pin1（细胞周期的重要调节剂）的潜在抑制剂中。顺式模拟物（Z）-烯烃异构体是通过使用Still-Wittig [2,3]-σ重排而形成的，而反式模拟物（E）-烯烃则是通过使用爱尔兰-克莱森[3,3]-σ重排。从N-Boc-Ser（OBn）-N（OMe）Me开始，两种模拟物均以适合肽合成的Boc保护形式合成，其中顺式模拟物的10步总产率为20％，八步中的总产率为13％。为反式模仿。

  DOI：

  10.1021/jo026663b

文献信息

• [EN] ALKENE MIMICS<br/>[FR] ANALOGUES D'ALCENES
  申请人：VIRGINIA TECH INTELL PROP

  公开号：WO2006020417A3

  公开（公告）日：2006-07-13
• A phosphorylated prodrug for the inhibition of Pin1
  作者：Song Zhao、Felicia A. Etzkorn

  DOI：10.1016/j.bmcl.2007.09.073

  日期：2007.12

  Fmoc-pSer-psi[(Z)CH = C]-Pro-(2)-N-(3)-ethylaminoindole 1, showed moderate inhibition towards the mitotic regulator, Pin1 (IC50 = 28.3 mu M). To improve the cell permeability, the charged phosphate was masked as the bis-pivaloyloxymethyl (POM) phosphate in Fmoc-(bisPOM)-pSer-psi[(Z)CH = C]-Pro-(2)-N-(3)-ethylaminoindole 2. Antiproliferative activity towards A2780 ovarian cancer cells of 1 (IC50 = 46.2 mu M) was improved significantly in 2 (IC50 = 26.9 mu M), comparable to the IC50 of 1 towards Pin1 enzymatic activity. (c) 2007 Elsevier Ltd. All rights reserved.
• Alkene Mimics
  申请人：Etzkorn Felicia A.

  公开号：US20080261923A1

  公开（公告）日：2008-10-23

  Ac-Phe-Tyr-phosphoSer-Ψ[CH═C]-Pro-Arg-NH 2 AND Fmoc-bis(pivaloylmethoxy)phosphoSer-Ψ[CH═C]-Pro-2-aminoethyl-(3-indole); and their Phospho-(D)-serine stereoisomers are novel compounds. Ψ refers to a pseudo amide. Such novel compounds advantageously may be used as alkene mimics.
• Conformationally Locked Isostere of PhosphoSer−<i>cis</i>-Pro Inhibits Pin1 23-Fold Better than PhosphoSer−<i>trans</i>-Pro Isostere
  作者：Xiaodong J. Wang、Bailing Xu、Ashley B. Mullins、Freda K. Neiler、Felicia A. Etzkorn

  DOI：10.1021/ja046396m

  日期：2004.12.1

  Stereoisomeric cis and trans substrate analogues for Pint were designed and synthesized. The central phosphoSer-Pro core of the Pin1 substrate was replaced by cis and trans amide isosteres in Ac-Phe-Phe-pser-Psi[(Z and E)CH=C]-Pro-Arg-NH2, 1 and 2, peptidomimetics. They were synthesized on solid phase in 17% yield for the cis analogue 1, and 16% yield for the trans analogue 2. A second trans amide isostere with a C-terminal N-methylamide 3 was synthesized in 7% yield. The protease-coupled Pint assay showed that all three compounds inhibited the Pint peptidyl-prolyl isomerase (PPlase) enzymatic activity. The cis isostere 1 was 23 times more potent (K-i = 1.74 +/- 0.08 muM) than its trans counterpart 2 (K-i = 40 +/- 2 muM) in competitive inhibition of Pint. These results suggest that the catalytic site of Pin1 binds cis substrates more tightly in aqueous solution. Antiproliferative activity toward the A2780 human ovarian cancer cell line by the cis and trans analogues correlates with Pint inhibition results.
• Serine-<i>cis</i>-proline and Serine-<i>trans</i>-proline Isosteres:  Stereoselective Synthesis of (<i>Z</i>)- and (<i>E</i>)-Alkene Mimics by Still−Wittig and Ireland−Claisen Rearrangements
  作者：Xiaodong J. Wang、Scott A. Hart、Bailing Xu、Matthew D. Mason、John R. Goodell、Felicia A. Etzkorn

  DOI：10.1021/jo026663b

  日期：2003.3.1

  cycle. The cis mimic, the (Z)-alkene isomer, was formed through the use of a Still-Wittig [2,3]-sigmatropic rearrangement, while the trans mimic, the (E)-alkene, was synthesized through the use of an Ireland-Claisen [3,3]-sigmatropic rearrangement. Starting from N-Boc-Ser(OBn)-N(OMe)Me, both mimics were synthesized in Boc-protected form suitable for peptide synthesis with an overall yield of 20% in 10

  设计并立体选择性合成了两个新的Ser-cis-Pro和Ser-trans-Pro酰胺同分异构体，以掺入磷酸化依赖性肽基脯氨酰异构酶Pin1（细胞周期的重要调节剂）的潜在抑制剂中。顺式模拟物（Z）-烯烃异构体是通过使用Still-Wittig [2,3]-σ重排而形成的，而反式模拟物（E）-烯烃则是通过使用爱尔兰-克莱森[3,3]-σ重排。从N-Boc-Ser（OBn）-N（OMe）Me开始，两种模拟物均以适合肽合成的Boc保护形式合成，其中顺式模拟物的10步总产率为20％，八步中的总产率为13％。为反式模仿。