O-t-butyl serine benzyl ester | 113247-75-9

• 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: O-t-butyl serine benzyl ester
• 英文别名: H-Ser(tBu)-OBzl；benzyl (2S)-2-amino-3-[(2-methylpropan-2-yl)oxy]propanoate
• CAS: 113247-75-9
• 化学式: C₁₄H₂₁NO₃
• 分子量: 251.326
• InChiKey: CIGGWMOPYCGDPN-LBPRGKRZSA-N

物化性质

• 沸点：
  361.4±27.0 °C(Predicted)
• 密度：
  1.068±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O-t-butyl serine benzyl ester 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  Peptidomimetics for Targeting Protein–Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL

  摘要：

  MLL-fusion proteins, AF9 and ENL, play an essential role in the recruitment of DOT1L and the H3K79 hypermethylation of MLL target genes, which is pivotal for leukemogenesis. Blocking these interactions may represent a novel therapeutic approach for MLL-rearranged leukemia. Based on the 7 mer DOT1L peptide, a class of peptidomimetics was designed. Compound 21 with modified middle residues, achieved significantly improved binding affinities to AF9 and ENL, with K-D values of 15 nM and 57 nM, respectively. Importantly, 21 recognizes and binds to the cellular AF9 protein and effectively inhibits the AF9-DOT1L interactions in cells. Modifications of the N- and C-termini of 21 resulted in 28 with 2-fold improved binding affinity to AF9 and much decreased peptidic characteristics. Our study provides a proof-of-concept for development of nonpeptidic compounds to inhibit DOT1L activity by targeting its recruitment and the interactions between DOT1L and MLL-oncofusion proteins AF9 and ENL.

  DOI：

  10.1021/acsmedchemlett.8b00175
• 作为产物：
  描述：

  N-fluorenylmethoxycarbonyl-O-t-butyl serine benzyl ester 在 哌啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 O-t-butyl serine benzyl ester
  参考文献：
  名称：

  Peptidomimetics for Targeting Protein–Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL

  摘要：

  MLL-fusion proteins, AF9 and ENL, play an essential role in the recruitment of DOT1L and the H3K79 hypermethylation of MLL target genes, which is pivotal for leukemogenesis. Blocking these interactions may represent a novel therapeutic approach for MLL-rearranged leukemia. Based on the 7 mer DOT1L peptide, a class of peptidomimetics was designed. Compound 21 with modified middle residues, achieved significantly improved binding affinities to AF9 and ENL, with K-D values of 15 nM and 57 nM, respectively. Importantly, 21 recognizes and binds to the cellular AF9 protein and effectively inhibits the AF9-DOT1L interactions in cells. Modifications of the N- and C-termini of 21 resulted in 28 with 2-fold improved binding affinity to AF9 and much decreased peptidic characteristics. Our study provides a proof-of-concept for development of nonpeptidic compounds to inhibit DOT1L activity by targeting its recruitment and the interactions between DOT1L and MLL-oncofusion proteins AF9 and ENL.

  DOI：

  10.1021/acsmedchemlett.8b00175

文献信息

• METHOD FOR REMOVING FMOC GROUP
  申请人：Ajinomoto Co., Inc.

  公开号：US20140296483A1

  公开（公告）日：2014-10-02

  The present invention relates to a method of removing an Fmoc group, including a step of mixing a compound represented by the formula (I): HS-L-COOH  (I) wherein L is a C 1-8 alkylene group optionally having substituent(s), an amino group-containing compound protected by an Fmoc group, and a base to give a reaction mixture containing a compound represented by the formula (II): Fm-S-L-COOH  (II) wherein Fm is a 9-fluorenylmethyl group, and L is as mentioned above, and an amino group-containing compound, and a step of removing the compound represented by the formula (II) by washing the obtained reaction mixture with a basic aqueous solution. According to the present invention, a removal method of Fmoc group, which can remove a dibenzofulvene derivative as a byproduct with ease, can be provided.

  本发明涉及一种去除Fmoc基团的方法，包括混合式化合物（I）的步骤：HS-L-COOH（I），其中L是一个C1-8烷基链，可选地具有取代基，一种被Fmoc基团保护的氨基化合物和一种碱，以得到一种反应混合物，其中包含一种化合物，其由式（II）表示：Fm-S-L-COOH（II），其中Fm是9-芴甲基基团，L如上所述，还包括一种氨基化合物，以及通过用碱性水溶液洗涤所得到的反应混合物，去除由式（II）表示的化合物。根据本发明，可以提供一种可以轻松去除二苯并富烯衍生物作为副产物的Fmoc基团去除方法。
• Method for removing FMOC group
  申请人：Ajinomoto Co., Inc.

  公开号：US09334302B2

  公开（公告）日：2016-05-10

  The present invention relates to a method of removing an Fmoc group, including a step of mixing a compound represented by the formula (I): HS-L-COOH  (I) wherein L is a C1-8 alkylene group optionally having substituent(s), an amino group-containing compound protected by an Fmoc group, and a base to give a reaction mixture containing a compound represented by the formula (II): Fm—S-L-COOH  (II) wherein Fm is a 9-fluorenylmethyl group, and L is as mentioned above, and an amino group-containing compound, and a step of removing the compound represented by the formula (II) by washing the obtained reaction mixture with a basic aqueous solution. According to the present invention, a removal method of Fmoc group, which can remove a dibenzofulvene derivative as a byproduct with ease, can be provided.

  本发明涉及一种去除Fmoc基团的方法，包括以下步骤：将式(I)所代表的化合物HS-L-COOH（式中L为C1-8烷基，可选地带有取代基，且为含有Fmoc基团保护的氨基化合物）与碱混合，得到反应混合物，其中反应混合物包含式(II)所代表的化合物Fm-S-L-COOH（式中Fm为9-芴甲基基团，L与上述相同，且为含有氨基的化合物）以及含有氨基的化合物；通过用碱性水溶液洗涤得到的反应混合物来去除式(II)所代表的化合物。根据本发明，可以提供一种去除Fmoc基团的方法，该方法可以轻松去除二苯基富烯衍生物作为副产物。
• Davies, John S.; Tremeer, E. John; Treadgold, Richard C., Journal of the Chemical Society. Perkin transactions I, 1987, p. 1107 - 1116
  作者：Davies, John S.、Tremeer, E. John、Treadgold, Richard C.

  DOI：——

  日期：——
• Influence of steric parameters on the synthesis of tetramates from α-amino-β-alkoxy-esters and Ph3PCCO
  作者：Inga Loke、Natja Park、Karl Kempf、Carsten Jagusch、Rainer Schobert、Sabine Laschat

  DOI：10.1016/j.tet.2011.10.099

  日期：2012.1

  alpha-Aminoesters react with Ph3PCCO in a domino addition-Wittig cyclization sequence affording enantiomerically pure tetramates. In the case of beta-oxo functionalized alpha-aminoesters, e.g., esters of serine, threonine or beta-hydroxyornithine the yields of this reaction depend heavily on the bulkiness of the beta-OR group and on the configuration of beta-carbon atom C-3. Smaller residues and 2R/3R-configured aminoesters give better yields. The alkoxycarbonyl group of the ester moiety and the residue on the N-atom are less important. These findings can be accounted for by assuming an early puckered transition state for the intramolecular ring-closing Wittig reaction. The addition of sub-stoichiometric amounts of benzoic acid or N-hydroxysuccinimide (for acid-sensitive compounds) is advantageous in some cases as it accelerates the formation of the intermediate amide ylides. (C) 2011 Elsevier Ltd. All rights reserved.
• Glycopeptide probes for understanding peptide specificity of the folding sensor enzyme UGGT
  作者：Takaya Kudo、Makoto Hirano、Toshihiro Ishihara、Shun Shimura、Kiichiro Totani

  DOI：10.1016/j.bmcl.2014.11.013

  日期：2014.12

  A systematic series of chitobiose-modified pentapeptides with sequence variations of hydrophobic leucine and hydrophilic serine were synthesized. The resulting glycopeptides were used as molecular probes to elucidate aglycon peptide specificity of the glycoprotein-folding sensor enzyme UGGT. Inhibitory experiments with a synthetic fluorescent glyco-substrate and the glycopeptides revealed that UGGT prefers a serine residue directly linked to C-terminal of the N-glycosylation site in its substrate recognition. (C) 2014 Elsevier Ltd. All rights reserved.