(S)-2-{1-benzyl-2-[(tert-butoxy)carbonyl]hydrazino}-3-methylbutanoic acid | 188777-46-0

• 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: (S)-2-{1-benzyl-2-[(tert-butoxy)carbonyl]hydrazino}-3-methylbutanoic acid
• 英文别名: N-benzyl-N-(tert-butoxycarbonylamino)-L-valine；Boc-NH(Bzl)Val；(2S)-2-[benzyl-[(2-methylpropan-2-yl)oxycarbonylamino]amino]-3-methylbutanoic acid
• CAS: 188777-46-0
• 化学式: C₁₇H₂₆N₂O₄
• 分子量: 322.404
• InChiKey: RKZZGYFHBIAYAT-AWEZNQCLSA-N

物化性质

• 熔点：
  108-112 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-{1-benzyl-2-[(tert-butoxy)carbonyl]hydrazino}-3-methylbutanoic acid 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 5.0~25.0 ℃ 、101.33 kPa 条件下， 反应 112.0h， 生成 Z-Ala-Ala-Pro-NHVal-Ala-Ala-NHⁱPr
  参考文献：
  名称：

  Design and Synthesis of Hydrazinopeptides and Their Evaluation as Human Leukocyte Elastase Inhibitors

  摘要：

  The name hydrazinopeptide designates peptidic structures in which one of the native CONH links is replaced by a CONHNH (hydrazido) fragment. In this paper, we report the synthesis of such hydrazinohexapeptides (3-5) analogous to Z-Ala-Ala-Pro-Val-Ala-Ala-(NHPr)-Pr-i (6), a substrate of human leukocyte elastase (HLE; EC 3.4.21.37), cleaved by this serine protease between the Val4 and Ala5 residues. In hydrazinopeptides 3-5, the Ala5, Val4, or Pro3 residue, respectively, of the model peptide, has been replaced by the corresponding alpha-L-hydrazino acid. In 3, the bond likely to be cleaved by HLE is the one involving the CONHNH link, while in 4 and 5, this link is normally shifted away by one or two amino acid units from the catalytic serine. On incubation with HLE, hydrazinopeptide 3 proved to be a substrate and was cleaved between Val4 and NHAla5, like peptide 6. In contrast, 4 and 5 proved to bind to HLE without being cleaved, featuring properties consistent with reversible competitive inhibition. General guidelines for the synthesis of hydrazinopeptides are also reported in this paper. These guidelines take into account the chemical specificity of hydrazino acids, while being fully compatible with the conventional peptide coupling techniques. The utilization of orthogonally bisprotected hydrazino acids 1 where the N-beta and N-alpha atoms bear a Boc and a Bzl group, respectively, is recommended for the easy construction of such hydrazinopeptides.

  DOI：

  10.1021/jm980419o
• 作为产物：
  描述：

  N-BOC-脒三苯基膦 在 LiMCPBA 、 四乙基氢氧化铵 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 19.0h， 生成 (S)-2-{1-benzyl-2-[(tert-butoxy)carbonyl]hydrazino}-3-methylbutanoic acid
  参考文献：
  名称：

  N-Alkyloxycarbonyl-3-aryloxaziridines: Their Preparation, Structure, and Utilization As Electrophilic Amination Reagents

  摘要：

  AbstractThis paper reports the synthesis of a series of N‐protected oxaziridines (N‐Moc, Boc, Z or Fmoc) and discusses their ability to deliver their N‐alkoxycar‐bonyl fragment to amines, enolates, sulfur, and phosphorus nucleophiles (electrophilic amination). These oxaziridines are prepared by oxidation of the corresponding imines with oxone or anhydrous MCPBA lithium salt as the source of oxygen. They transfer their N‐protected fragment to primary and secondary amines to give protected hydrazines in fair to excellent yield. The nitrogen transfer to free amino acids (in form of their R4N+ salts) is particularly fast, even at low temperature, providing L (or D) N‐protected α‐hydrazino acids. Enolates are C‐aminated to give N‐protected α‐amino ketones, esters, or amides in modest yield, due to a side aldol reaction of the unreacted enolate with the released benzaldehyde. With tertiary amines (Et3N), sulfides (PhSMe), and phosphines (Ph3P), amination and oxidation proceed in a parallel way; the amount of amination product increases when the temperature is lowered (kinetic control). Some of the factors that can orient the oxaziridine reactivity towards amination or oxidation of nucleophiles are considered.

  DOI：

  10.1002/chem.19970031019

文献信息

• Multicomponent synthesis of hydrazino depsipeptides
  作者：Josipa Suć、Danijela Barić、Ivanka Jerić

  DOI：10.1039/c6ra23317a

  日期：——

  The Passerini reaction of α-hydrazino acids, carbonyl compounds and isocyanides yielded hydrazino depsipeptides, a new class of backbone extended peptidomimetics comprising amide bond isostere. A wide range of carbonyl and isocyano components were used along the α-hydrazino acids carrying three different Nα protecting groups. The kinetics and thermodynamic equilibrium of the rate-determining step of

  α-肼基酸，羰基化合物和异氰酸酯的Passerini反应产生肼基二肽，这是一类新型的骨架扩展的拟肽，包括酰胺键等排物。宽范围的羰基和异氰基部件被沿着携带三种不同的α肼羧酸使用Ñ α保护基团。通过DFT方法研究了与不同的α-肼基酸反应的速率决定步骤的动力学和热力学平衡。
• Synthesis, CD Spectra, and Enzymatic Stability ofβ2-Oligoazapeptides Prepared from (S)-2-Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and Leu
  作者：Gérald Lelais、Dieter Seebach

  DOI：10.1002/hlca.200390342

  日期：2003.12

  solvents), it was not possible to determine the secondary structure of the β2-azapeptides by NMR spectroscopy (overlapping and broad signals, fast exchange between the two types of NH protons!). The CD spectra of the N-Boc and C-OMe terminally protected hexapeptide analog 9 in MeOH and in H2O (at different pH) might arise from a (P)-314-helical structure. The N-Boc-β2-tri and N-Boc-β2-hexaazapeptide esters

  β-肽提供了将其他杂原子掺入肽主链的独特可能性（图1和2）。我们在这里报告的合成和光谱研究的β 2个选自（的自身肽类似物小号）-3-氮杂- β -氨基酸携带缬氨酸，丙氨酸，和Leu的侧链。通过已知方法制备肼基甲酸：将相应的N-苄基-L - α-氨基酸与恶唑烷进行Boc酰胺化（方案1）。联接器和片段3 benzylaza-的耦合β 2 -氨基酸和相应的三肽（Ñ-Boc / Ç -OMe策略）与溶液中导致常见的肽偶联试剂β 2 -二，β 2 -三- ，和β 2个-hexaazapeptide衍生物，其可以是Ñ -debenzylated（4 - 9 ;方案2- 4）。通过旋光，IR，1 H和13 C-NMR，CD光谱（图4和5）和高分辨率质谱鉴定新化合物，在一种情况下，通过X射线晶体学鉴定（图3）。尽管各种条件（温度，溶剂）下广泛的测量，这是不可能的，以确定的二级结构β 2个通过NMR光谱-a
• Electrophilic Amination of Amino Acids with N-Boc-oxaziridines:  Efficient Preparation of N-Orthogonally Diprotected Hydrazino Acids and Piperazic Acid Derivatives
  作者：Jean-Christophe Hannachi、Joëlle Vidal、Jean-Christophe Mulatier、André Collet

  DOI：10.1021/jo035700b

  日期：2004.4.1

  preparation of enantiopure Nα,Nβ-orthogonally diprotected α-hydrazino acids 1 is developed on a multigram scale. The key reaction is the efficient electrophilic amination of N-benzyl amino acids 6 with N-Boc-oxaziridine 7 and accommodates various functional groups encountered in side chains of amino acids. The cyclic 2,3,4,5-tetrahydro-3-pyridazine carboxylic acid (piperazic acid) derivatives 2 and 3 or

  对映体纯n的一般两步制备α，N β -orthogonally双保护的α-肼基酸1是在多克规模开发的。关键反应是将N-苄基氨基酸6与N -Boc-恶唑烷7进行有效的亲电胺化反应，并容纳氨基酸侧链中遇到的各种官能团。环状2,3,4,5-四氢-3-哒嗪羧酸（哌嗪酸）衍生物2和3或环状3,4-二氢-3-吡唑羧酸酯4方便地由谷氨酸或天冬氨酸经正交双保护制备。 α-肼基酸1m和1n。
• N-Alkyloxycarbonyl-3-aryloxaziridines: Their Preparation, Structure, and Utilization As Electrophilic Amination Reagents
  作者：Joëlle Vidal、Stéphanie Damestoy、Laure Guy、Jean-Christophe Hannachi、André Aubry、Andreé Collet、André Aubry

  DOI：10.1002/chem.19970031019

  日期：1997.10

  AbstractThis paper reports the synthesis of a series of N‐protected oxaziridines (N‐Moc, Boc, Z or Fmoc) and discusses their ability to deliver their N‐alkoxycar‐bonyl fragment to amines, enolates, sulfur, and phosphorus nucleophiles (electrophilic amination). These oxaziridines are prepared by oxidation of the corresponding imines with oxone or anhydrous MCPBA lithium salt as the source of oxygen. They transfer their N‐protected fragment to primary and secondary amines to give protected hydrazines in fair to excellent yield. The nitrogen transfer to free amino acids (in form of their R4N+ salts) is particularly fast, even at low temperature, providing L (or D) N‐protected α‐hydrazino acids. Enolates are C‐aminated to give N‐protected α‐amino ketones, esters, or amides in modest yield, due to a side aldol reaction of the unreacted enolate with the released benzaldehyde. With tertiary amines (Et3N), sulfides (PhSMe), and phosphines (Ph3P), amination and oxidation proceed in a parallel way; the amount of amination product increases when the temperature is lowered (kinetic control). Some of the factors that can orient the oxaziridine reactivity towards amination or oxidation of nucleophiles are considered.
• Design and Synthesis of Hydrazinopeptides and Their Evaluation as Human Leukocyte Elastase Inhibitors
  作者：Laure Guy、Joëlle Vidal、André Collet、Augustin Amour、Michèle Reboud-Ravaux

  DOI：10.1021/jm980419o

  日期：1998.11.1

  The name hydrazinopeptide designates peptidic structures in which one of the native CONH links is replaced by a CONHNH (hydrazido) fragment. In this paper, we report the synthesis of such hydrazinohexapeptides (3-5) analogous to Z-Ala-Ala-Pro-Val-Ala-Ala-(NHPr)-Pr-i (6), a substrate of human leukocyte elastase (HLE; EC 3.4.21.37), cleaved by this serine protease between the Val4 and Ala5 residues. In hydrazinopeptides 3-5, the Ala5, Val4, or Pro3 residue, respectively, of the model peptide, has been replaced by the corresponding alpha-L-hydrazino acid. In 3, the bond likely to be cleaved by HLE is the one involving the CONHNH link, while in 4 and 5, this link is normally shifted away by one or two amino acid units from the catalytic serine. On incubation with HLE, hydrazinopeptide 3 proved to be a substrate and was cleaved between Val4 and NHAla5, like peptide 6. In contrast, 4 and 5 proved to bind to HLE without being cleaved, featuring properties consistent with reversible competitive inhibition. General guidelines for the synthesis of hydrazinopeptides are also reported in this paper. These guidelines take into account the chemical specificity of hydrazino acids, while being fully compatible with the conventional peptide coupling techniques. The utilization of orthogonally bisprotected hydrazino acids 1 where the N-beta and N-alpha atoms bear a Boc and a Bzl group, respectively, is recommended for the easy construction of such hydrazinopeptides.