ethyl (3S)-4-methyl-3-(N-tert-butylcarbonyloxy)amino-2,2-difluoropentanoate | 676460-38-1

• 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: ethyl (3S)-4-methyl-3-(N-tert-butylcarbonyloxy)amino-2,2-difluoropentanoate
• 英文别名: ethyl (3S)-3-[(tert-butoxycarbonyl)amino]-2,2-difluoro-4-methylpentanoate；ethyl (S)-3-((tert-butoxycarbonyl)amino)-2,2-difluoro-4-methylpentanoate
• CAS: 676460-38-1
• 化学式: C₁₃H₂₃F₂NO₄
• 分子量: 295.327
• InChiKey: ZTHUARFRJGHBLZ-VIFPVBQESA-N

物化性质

• 沸点：
  348.5±42.0 °C(Predicted)
• 密度：
  1.091±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl (3S)-4-methyl-3-(N-tert-butylcarbonyloxy)amino-2,2-difluoropentanoate 在 {(π-CH2CHCH2)PdCl}2 、 1,3-双(二苯基膦)丙烷 、 苯硅烷 、 二异丁基氢化铝 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 8.83h， 生成 ethyl (5S,3Z)-5-[N-(tert-butoxycarbonyl)amino]-4-fluoro-6-methylhept-3-enoate
  参考文献：
  名称：

  单氟烯烃-等排体作为肽骨架的19 F NMR标记：在膜结合的PGLa和（KIGAKI）3中合成和评估。

  摘要：

  固态19 F NMR是研究生物活性肽与膜相互作用的有力方法。到目前为止，在标记的肽中，19 F-报告基团一直被安装在氨基酸的侧链上。考虑到单氟烯烃是不可水解的肽键模拟物，我们合成了基于单氟烯烃的二肽等位物Val-Ψ[（Z）-CF = CH] -Gly，并将其插入到两个经过充分研究的抗菌素序列中肽：PGLa和（KIGAKI）3是α-螺旋和β-折叠的代表。研究了这些标记肽的构象和生物学活性，以评估一氟烯烃对19 F NMR结构分析的适用性。

  DOI：

  10.1002/chem.201905054
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 ethyl (S)-2,2-difluoro-3-(((R)-2-methoxy-1-phenylethyl)amino)-4-methylpentanoate 在 10 wt% Pd(OH)2 on carbon 、 氢气 作用下， 以 乙醇 、 四氢呋喃 为溶剂， 反应 10.0h， 以71%的产率得到ethyl (3S)-4-methyl-3-(N-tert-butylcarbonyloxy)amino-2,2-difluoropentanoate
  参考文献：
  名称：

  单氟烯烃-等排体作为肽骨架的19 F NMR标记：在膜结合的PGLa和（KIGAKI）3中合成和评估。

  摘要：

  固态19 F NMR是研究生物活性肽与膜相互作用的有力方法。到目前为止，在标记的肽中，19 F-报告基团一直被安装在氨基酸的侧链上。考虑到单氟烯烃是不可水解的肽键模拟物，我们合成了基于单氟烯烃的二肽等位物Val-Ψ[（Z）-CF = CH] -Gly，并将其插入到两个经过充分研究的抗菌素序列中肽：PGLa和（KIGAKI）3是α-螺旋和β-折叠的代表。研究了这些标记肽的构象和生物学活性，以评估一氟烯烃对19 F NMR结构分析的适用性。

  DOI：

  10.1002/chem.201905054

文献信息

• Diastereoselective synthesis of highly functionalized fluoroalkene dipeptide isosteres and its application to Fmoc-based solid-phase synthesis of a cyclic pentapeptide mimetic
  作者：Tetsuo Narumi、Kenji Tomita、Eriko Inokuchi、Kazuya Kobayashi、Shinya Oishi、Hiroaki Ohno、Nobutaka Fujii

  DOI：10.1016/j.tet.2008.02.076

  日期：2008.5

  A diastereoselective and divergent method for synthesis of a highly functionalized (Z)-fluoroalkene dipeptide isosteres has been developed. The key feature of this synthetic method is an efficient one-pot reaction involving reduction/asymmetric alkylation via transmetalation, which produces trans-amide type (Z)-fluoroalkenes flanking two stereogenic centers in high yields, with excellent (Z)-selectivity

  已经开发了用于合成高度官能化的（Z）-氟代烯烃二肽等排体的非对映选择性和发散方法。该合成方法的关键特征是有效的一锅反应，涉及通过金属转移进行的还原/不对称烷基化反应，该反应可高产率地产生侧接两个立构中心的反酰胺型（Z）-氟代烯烃，并具有出色的（Z）选择性和非对映选择性。还描述了实用的基于Fmoc的固相合成特定的CXCR4拮抗假肽25，该肽含有（Z）-氟烯烃等排异构体。
• Diastereoselective Synthesis of Aliphatic α,α-Difluoro-β³-Amino Esters via a Sonocatalyzed Reformatsky Reaction
  作者：Taryn L. March、Martin R. Johnston、Peter J. Duggan

  DOI：10.1021/ol202969w

  日期：2012.1.6

  (R)-2-Phenylglycine ethyl ester was found to be a cheap and effective auxiliary for the preparation of aliphatic α,α-difluoro-β3-amino esters via a Reformatsky reaction performed under sonication conditions. The products were obtained in good to high yield and ≥96:4 dr, thus providing a new stereoselective route to this under-represented class of compounds. A facile one-pot removal of the phenylglycine

  （- [R）-2-苯基甘氨酸乙酯被发现是一种廉价和有效的辅助为脂族α的制备中，α二氟β 3经由reformatsky反应-氨基酯超声处理条件下进行。获得的产品具有良好的高收率和≥96：4 dr，因此为此类代表性不足的化合物提供了新的立体选择性途径。一种简便一锅除去苯基甘氨酸部分和伴随的Boc保护的随后得到相应的Boc保护的β 3 -氨基酯的优良率。
• A novel one-pot reaction involving organocopper-mediated reduction/transmetalation/asymmetric alkylation, leading to the diastereoselective synthesis of functionalized (Z)-fluoroalkene dipeptide isosteres
  作者：Tetsuo Narumi、Ayumu Niida、Kenji Tomita、Shinya Oishi、Akira Otaka、Hiroaki Ohno、Nobutaka Fujii

  DOI：10.1039/b608596b

  日期：——

  By a novel one-pot reaction sequence involving consecutive organocopper-mediated reduction, transmetalation and asymmetric alkylation, a highly diastereoselective synthesis of functionalized (Z)-fluoroalkene dipeptide isosteres was achieved in good to excellent yields.

  通过涉及连续的有机铜介导的还原，过渡金属化和不对称烷基化的新颖的一锅式反应序列，以良好至优异的产率实现了官能化的（Z）-氟代烯烃二肽等排体的高度非对映选择性合成。
• SmI₂-Mediated Reduction of γ,γ-Difluoro-α,β-enoates with Application to the Synthesis of Functionalized (<i>Z</i>)-Fluoroalkene-Type Dipeptide Isosteres
  作者：Akira Otaka、Junko Watanabe、Akira Yukimasa、Yoshikazu Sasaki、Hideaki Watanabe、Takayoshi Kinoshita、Shinya Oishi、Hirokazu Tamamura、Nobutaka Fujii

  DOI：10.1021/jo035709d

  日期：2004.3.1

  A samarium diiodide (SmI2)-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the gamma,gamma-difluoro-alpha,beta-enoates by SmI2 proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to a-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI2-HCHO reagent system with chiral enoate 34 provided D-Phe-psi[(Z)-CF=CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the a-position. This was achieved by a sequence of manipulations consisting of beta-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of alpha,alpha-difluoro-beta-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.