N-fluorenylmethoxycarbonyl-O-t-butyl serine benzyl ester | 73724-47-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-fluorenylmethoxycarbonyl-O-t-butyl serine benzyl ester
• 英文别名: L-N-Fmoc-(O-tBu)-serine benzyl ester；benzyl (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoate
• CAS: 73724-47-7
• 化学式: C₂₉H₃₁NO₅
• 分子量: 473.569
• InChiKey: NJDVXPKUKMUQTJ-SANMLTNESA-N

物化性质

• 沸点：
  648.2±55.0 °C(Predicted)
• 密度：
  1.180±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  苯甲醇 、 Fmoc-Ser(tBu)-OMe 在 iron(III)-acetylacetonate 作用下， 以 正庚烷 为溶剂， 反应 13.0h， 以96%的产率得到N-fluorenylmethoxycarbonyl-O-t-butyl serine benzyl ester
  参考文献：
  名称：

  Transesterification catalyzed by iron(III) β-diketonate species

  摘要：

  A practical and clean protocol for transesterification catalyzed by a 5 mol % cheap, non-toxic and moisture stable Fe(acac)(3) or other iron(III) beta-diketonate species in solvent, such as heptane under azeotropic condition is developed. A remarkable rate enhancement was observed upon the addition of 5 mol % of an inorganic base, such as Na2CO3, which suggests that faster formation of a dimeric mu-alkoxy-bridged iron (III) species under alkaline conditions facilitates catalytic turnover. This system provides smooth transesterification over a wide range of structurally diverse esters and alcohols without disturbing functional groups. In addition, the use of iron beta-diketonate complexes as catalysts is more environmentally friendly, safer, and economical than other transition-metal catalysts. Preliminary mechanistic studies indicate that the active catalyst is likely a dimeric mu-alkoxy-bridged iron(III) species, as determined by X-ray crystallography of [Fe(dbm)(2)(O-n-Bu)](2) derived from the alcoholysis of Fe(dbm)(3) under alkaline conditions. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.01.009

文献信息

• Direct Esterification of Carboxylic Acids with Alcohols Catalyzed by Iron(III) Acetylacetonate Complex
  作者：Shiue-Shien Weng、Fong-Kuang Chen、Chih-Shueh Ke

  DOI：10.1080/00397911.2012.725265

  日期：2013.10.2

  Abstract Direct condensation of carboxylic acids and alcohols with electronic, steric, and functional group variations was carried out using the environmentally benign, moisture-stable, inexpensive, and recoverable iron(III) acetylacetonate [Fe(acac)3] as catalyst (5 mol%). This iron salt efficiently catalyzed the esterification of several primary and secondary alcohols in refluxing xylene, without the need

  摘要 使用环境友好、耐湿、廉价且可回收的乙酰丙酮铁 (III) [Fe(acac)3] 作为催化剂 (5 mol) 进行具有电子、空间和官能团变化的羧酸和醇的直接缩合反应。 %）。这种铁盐有效地催化了回流二甲苯中几种伯醇和仲醇的酯化反应，而无需脱水试剂。通过用苯甲酸对外消旋 1-苯基乙烷-1,2-二醇中的伯醇官能团进行选择性酯化，证明了所提议方案的化学选择性。酯化也适用于未掩蔽的 α-羟基酸、guasaromatic、杂环和 N-保护的氨基酸。补充材料可用于本文。去出版商' 的 Synthetic Communications® 在线版以查看免费的补充文件。图形概要
• 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：——
• Peptidomimetics for Targeting Protein–Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL
  作者：Lei Du、Sierrah M. Grigsby、Aihong Yao、Yujie Chang、Garrett Johnson、Haiying Sun、Zaneta Nikolovska-Coleska

  DOI：10.1021/acsmedchemlett.8b00175

  日期：2018.9.13

  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.
• Transesterification catalyzed by iron(III) β-diketonate species
  作者：Shiue-Shien Weng、Chih-Shueh Ke、Fong-Kuang Chen、You-Fu Lyu、Guan-Ying Lin

  DOI：10.1016/j.tet.2011.01.009

  日期：2011.3

  A practical and clean protocol for transesterification catalyzed by a 5 mol % cheap, non-toxic and moisture stable Fe(acac)(3) or other iron(III) beta-diketonate species in solvent, such as heptane under azeotropic condition is developed. A remarkable rate enhancement was observed upon the addition of 5 mol % of an inorganic base, such as Na2CO3, which suggests that faster formation of a dimeric mu-alkoxy-bridged iron (III) species under alkaline conditions facilitates catalytic turnover. This system provides smooth transesterification over a wide range of structurally diverse esters and alcohols without disturbing functional groups. In addition, the use of iron beta-diketonate complexes as catalysts is more environmentally friendly, safer, and economical than other transition-metal catalysts. Preliminary mechanistic studies indicate that the active catalyst is likely a dimeric mu-alkoxy-bridged iron(III) species, as determined by X-ray crystallography of [Fe(dbm)(2)(O-n-Bu)](2) derived from the alcoholysis of Fe(dbm)(3) under alkaline conditions. (C) 2011 Elsevier Ltd. All rights reserved.