methyl 3-(R)-[N-(tert-butoxycarbonyl)amino]-4-methylpentanoate | 511550-54-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 3-(R)-[N-(tert-butoxycarbonyl)amino]-4-methylpentanoate
• 英文别名: (S)-methyl 3-(tert-butoxycarbonyl)-4-methylpentanoate；Boc-(S)-β3hVal methyl ester；methyl (S)-3-((tert-butoxycarbonyl)amino)-4-methylpentanoate；methyl (3S)-4-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 511550-54-2
• 化学式: C₁₂H₂₃NO₄
• 分子量: 245.319
• InChiKey: HJFMEBROZSGPLZ-VIFPVBQESA-N

物化性质

• 沸点：
  329.6±25.0 °C(Predicted)
• 密度：
  1.008±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(R)-[N-(tert-butoxycarbonyl)amino]-4-methylpentanoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以89%的产率得到S-3-Boc-氨基-4-甲基戊酸
  参考文献：
  名称：

  A Convenient Synthesis of Chiral β³-Amino Acids

  摘要：

  开发了一种合成手性β3-氨基酸的新方法，其中酸功能团是通过氧化断裂引入的α-烯丙基，该基团由Evans不对称烷基化适当的酸底物引入，而氨基部分则来自原始羧基的酰胺，经过改良的Hofmann重排反应后形成。

  DOI：

  10.1055/s-2002-35608
• 作为产物：
  描述：

  异丁酰醋酸甲酯 在 [Ph(COD)Cl]2 (R,S)-tert-butyl Josiphos 、 ammonium acetate 、 氢气 作用下， 以 甲醇 为溶剂， 20.0~50.0 ℃ 、689.47 kPa 条件下， 反应 42.0h， 生成 methyl 3-(R)-[N-(tert-butoxycarbonyl)amino]-4-methylpentanoate
  参考文献：
  名称：

  检测和消除烯胺的不对称催化氢化产生的产物抑制作用。

  摘要：

  [反应：见正文]通过动力学研究表明，由二茂铁基配体1a或1b和[（COD）RhCl]（2）制备的用催化剂Rh-1a催化烯胺酰胺和酯的催化不对称加氢反应抑制。还显示烯胺酯底物与在甲醇中反应的胺产物不相容。用二碳酸二叔丁酯原位保护胺产物消除了酯底物的官能团不相容性，并消除了反应中产物的抑制作用。

  DOI：

  10.1021/ol051862d

文献信息

• A Convenient Synthesis of Chiral β³-Amino Acids
  作者：Tushar K. Chakraborty、Animesh Ghosh

  DOI：10.1055/s-2002-35608

  日期：——

  A novel method for the synthesis of chiral β3-amino acids is developed where the acid functionality was built by oxidative cleavage of an α-allylic group that was introduced by Evans’ asymmetric alkylation of an appropriate acid substrate and the amino part came from the amide of the original carboxyl group following a modified Hofmann rearrangement reaction.

  开发了一种合成手性β3-氨基酸的新方法，其中酸功能团是通过氧化断裂引入的α-烯丙基，该基团由Evans不对称烷基化适当的酸底物引入，而氨基部分则来自原始羧基的酰胺，经过改良的Hofmann重排反应后形成。
• Catalytic Asymmetric Mannich Reactions of Sulfonylacetates
  作者：Carlo Cassani、Luca Bernardi、Francesco Fini、Alfredo Ricci

  DOI：10.1002/anie.200900701

  日期：2009.7.20

  synthetic equivalents of a variety of α‐carboxylate anions. Phase‐transfer catalysis (PTC) enabled their mild deprotonation and catalytic asymmetric addition to highly reactive imines generated in situ from α‐amidosulfones (see scheme; Pg=protecting group). The synthetic utility of the products was demonstrated by their straightforward transformation into a range of β‐amino acid derivatives.

  砜与砜：芳基磺酰乙酸盐可以看成是各种α-羧酸根阴离子的合成等价物。相转移催化（PTC）使它们能够轻度去质子化，并催化不对称添加到α-酰胺基砜现场生成的高反应性亚胺上（见方案； Pg =保护基）。通过将其直接转化为一系列β-氨基酸衍生物，证明了该产品的合成效用。
• Optimization of the β-Aminoester class of factor Xa inhibitors. part 1: P4 and side-Chain modifications for improved In vitro potency
  作者：Mark Czekaj、Scott I Klein、Kevin R Guertin、Charles J Gardner、Allison L Zulli、Henry W Pauls、Alfred P Spada、Daniel L Cheney、Karen D Brown、Dennis J Colussi、Valeria Chu、Robert J Leadley、Christopher T Dunwiddie

  DOI：10.1016/s0960-894x(02)00212-3

  日期：2002.6

  A systematic modification of the C3 side-chain of the beta-aminoester class of factor Xa inhibitors and a survey Of P-4 variations is described. These changes have resulted in the identification of sub-nanomolar inhibitors with improved selectivity versus related proteases. Coagulation parameters (i.e., APTT doubling concentrations) are also improved. (C) 2002 Elsevier Science Ltd. All rights reserved.
• CD Spectra in Methanol ofβ-Oligopeptides Consisting ofβ-Amino Acids with Functionalized Side Chains, with Alternating Configuration, and with Geminal Backbone Substituents - Fingerprints of New Secondary Structures?
  作者：Dieter Seebach、Thierry Sifferlen、Pascal A. Mathieu、Andreas M. Häne、Christoph M. Krell、Daniel J. Bierbaum、Stefan Abele

  DOI：10.1002/1522-2675(20001108)83:11<2849::aid-hlca2849>3.0.co;2-r

  日期：2000.11.8

  beta -Hexa-, beta -hepta-, and beta -nonapeptides, 1-6, which carry functionalized side chains (CO(2)R, CO(2)(-), (CH(2))(4)NH(3)(+), CH(2)-CH=CH(2)) consisting of beta (3)-amino-acid residues of alternating configuration, or which carry geminal substituents in the 2- or 3-positions of all residues, have been synthesized (Schemes 1 - 3), and their CD spectra in MeOH are reported (Figs. 2 - 6). Strong Cotton effects (Theta >10(5)) are indicative of the presence of chiral secondary structures. It is suggested by simple modelling (Fig. 1) that the new beta -peptides should not be able to fold to the familiar 3(14)-helical structures. Still, three of them (3, 4, and 5) give rise to CD spectra matching those of beta -peptides that are known to be present as (M)- or (P)3(14)-helices in MeOH solution. While possible folding motifs (Figs. 3, b, and 7) of the new beta -peptides have been identified in crystal structures, an interpretation of the CD spectra has to be postponed until NMR solution structures become available. A list of all beta -peptides giving rise to CD spectra with a minimum near 215 nm is included (Table).
• Detection and Elimination of Product Inhibition from the Asymmetric Catalytic Hydrogenation of Enamines
  作者：Karl B. Hansen、Thorsten Rosner、Michele Kubryk、Peter G. Dormer、Joseph D. Armstrong

  DOI：10.1021/ol051862d

  日期：2005.10.1

  text] The catalytic asymmetric hydrogenation of enamine amides and esters with catalyst Rh-1a, prepared from ferrocenyl based ligand 1a or 1b and [(COD)RhCl](2), has been shown through kinetic studies to suffer from product inhibition. Enamine ester substrates have also been shown to be incompatible with the amine products of the reaction in methanol. In situ protection of the amine products with di-tert-butyl

  [反应：见正文]通过动力学研究表明，由二茂铁基配体1a或1b和[（COD）RhCl]（2）制备的用催化剂Rh-1a催化烯胺酰胺和酯的催化不对称加氢反应抑制。还显示烯胺酯底物与在甲醇中反应的胺产物不相容。用二碳酸二叔丁酯原位保护胺产物消除了酯底物的官能团不相容性，并消除了反应中产物的抑制作用。