Cbz-Gly-L-Thr-OMe | 41961-03-9

• 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: Cbz-Gly-L-Thr-OMe
• 英文别名: Z-Gly-Thr-OMe；Cbz-Gly-Thr-OMe；methyl (2S,3R)-3-hydroxy-2-[[2-(phenylmethoxycarbonylamino)acetyl]amino]butanoate
• CAS: 41961-03-9
• 化学式: C₁₅H₂₀N₂O₆
• 分子量: 324.334
• InChiKey: FUONNQHEMRALBH-MFKMUULPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Cbz-Gly-L-Thr-OMe 在 ruthenium trichloride 、 sodium periodate 作用下， 以 四氯化碳 、 乙腈 为溶剂， 反应 8.0h， 以92%的产率得到N-苄氧羰基甘氨酰胺
  参考文献：
  名称：

  Protein Backbone Modification by Novel C.alpha.-C Side-Chain Scission

  摘要：

  alpha-Ketoamide (-NH-CO-CO-) units in intact peptides are generated from Ser/Thr residues via Ru(VIII)catalyzed C-alpha-C side-chain scission. Facets associated with this novel cu-carbon modification have been probed with 75 peptides chosen to represent every possible peptide environment. The reactions were carried out at room temperature with in situ generated Ru(VIII) in biphasic (CH3CN/CCl4/pH 3 phosphate buffer, 1:1:2 v/v) medium. Whereas Ser/Thr residues placed at the C-terminal end in peptides undergo N-C bond scission leading to des-Ser/Thr peptide amides-thus acting as Gly equivalents in simulating the alpha-amidating action of pituitary enzymes-those located at the N-terminal or nonterminal or even at the C-terminal position (protected as amide) were found to undergo oxidative C-C bond scission (involving C-alpha and C side-chain bond), resulting in the generation of alpha-ketoamide (-NH-CO-CO-) units in the intact peptide backbone. The difference in the products arising from C-alpha-C side-chain scission of Ser/Thr esters and amides is rationalized on the basis of a common mechanism involving either oxaloesters [Pep-NH-CO-COX; X = OMe] or oxalamides [X = NH2 or NH-Pep] arising from the oxidation of initially formed carbinolamide intermediates [Pep-NH-CH(OH)-COX],wherein, while the former are shown to undergo hydrolysis to terminal amides [Pep-NH2], the oxalamides are found to be stable to hydrolysis. Ancillary noteworthy findings are those of peptide bond scission when contiguous Ser-Ser/Thr-Thr residues are present and the oxidative cleavage at C-terminal Tyr/Trp sites generating des amides. The oxidative methodology presented here is mild, simple, and practical and proceeds with chiral retention. The insensitivity of a large number of amino acid residues, such as Gly, Ala, Leu, Asn, Gln, Asp, Glu, Pro, Arg, Phe, Lys, Val, and Aib, and N-protecting groups, such as Boc, Z, and Bz, toward Ru(VIII) under the experimental conditions should make this methodology practical and useful. Sulfur-containing amino acids Cys and Met get oxidized to sulfones in the products.

  DOI：

  10.1021/ja00094a008
• 作为产物：
  描述：

  L-苏氨酸甲酯盐酸盐 、 N-苄氧羰基甘氨酸 在 N-甲基吗啉 、 氯甲酸异丁酯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 以85%的产率得到Cbz-Gly-L-Thr-OMe
  参考文献：
  名称：

  N,O-Isopropylidenated Threonines as Tools for Peptide Cyclization:  Application to the Synthesis of Mahafacyclin B

  摘要：

  The influence of a single N,O-isopropylidenated threonine turn-inducer on the cyclization of a linear heptapeptide precursor to mahafacyclin B has been investigated. Incorporation of an N,O-isopropylidenated threonine more than doubles the head-to-tail cyclization yield. The N,O-isopropylidene grouping is then readily disassembled to give the antimalarial cyclic peptide in high yield.

  DOI：

  10.1021/ol0522891

文献信息

• Bromelain Catalyzed Synthesis of Peptides in Organic Solvent
  作者：Dar-Fu Tai、Shu-Lin Fu

  DOI：10.1002/jccs.200300025

  日期：2003.2

  exported by Taiwan. There is no deficiency for thesource of this enzyme. Therefore, the application of bro-melain to catalyze the synthesis of peptides has great poten-tial and economic value.No research effort has ever been made in peptide syn-thesis using bromelain except for catalyzing polymerizationin aqueous solution.

  是一种来自菠萝茎提取物的硫醇蛋白酶。菠萝是台湾丰富的资源。菠萝蛋白酶（EC.3,4,4,24）是台湾出口的两种主要酶之一。这种酶的来源没有缺陷。因此，将菠萝蛋白酶应用于催化多肽合成具有巨大的潜力和经济价值。除在水溶液中催化聚合外，目前还没有利用菠萝蛋白酶合成多肽的研究成果。
• Total Synthesis of the Proposed Microcyclamides MZ602 and MZ568
  作者：Yi Liu、Xiangyun Zhao、Hongbo Wang、Huili Liu、Zhuyin Sui、Bingfei Yan、Yuguo Du

  DOI：10.1021/acs.joc.0c02541

  日期：2021.1.1

  of the proposed natural microcyclamide MZ602, except to an opposite sign of the optical rotation value. Surprisingly, the synthetic MZ568 (2) presented large discrepancies in characteristic spectral data from those of the reported natural product, although the absolute configuration of key intermediate 36 was unambiguously determined by single-crystal X-ray analysis in our work. These findings revealed

  拟议结构的微环酰胺MZ602（1）和MZ568（2）的第一个收敛性全合成反应已通过11个线性步骤完成，总产率分别为12.5和16.8％。合成的关键特征包括一锅级联反应以构建核心Boc - 1 -Ile-Thz-OAllyl片段5，以及可移动的假脯氨酸（ΨMe ，Me pro）诱导剂辅助的含噻唑的all- 1线性肽环化。合成MZ602的光谱数据（1 H NMR，13 C NMR和HRMS）（1）与拟议的天然微环酰胺MZ602非常相似，除了旋光度值的符号相反。出人意料的是，尽管我们的工作通过单晶X射线分析明确确定了关键中间体36的绝对构型，但合成MZ568（2）在特征光谱数据上与报告的天然产物却存在较大差异。这些发现表明，天然微环酰胺MZ602和MZ568的拟议结构需要修改。
• Solid-State and Solution-Phase Conformations of Pseudoproline-Containing Dipeptides
  作者：Jack K. Clegg、James R. Cochrane、Nima Sayyadi、Danielle Skropeta、Peter Turner、Katrina A. Jolliffe

  DOI：10.1071/ch09151

  日期：——

  The conformations of 14 threonine-derived pseudoproline-containing dipeptides (including four d-allo-Thr derivatives) have been investigated by NMR. In solution, the major conformer observed for all dipeptides is that in which the amide bond between the pseudoproline and the preceding amino acid is cis. For dipeptides in which the N-terminus is protected, the ratio of cis- to trans-conformers does not depend significantly on the side chain of the N-terminal amino acid, or the stereochemistry of the Thr residue. However, for dipeptides bearing a free N-terminus, there are significant differences in the ratios of cis- to trans-conformers depending on the side chain present. Three dipeptides were crystallized and their X-ray structures determined. In two cases, (benzyloxycarbonyl (Cbz)-Val-Thr(ΨMe,Mepro)-OMe and Cbz-Val-Thr(ΨMe,Mepro)-OH), the dipeptides adopt a trans-conformation in the solid state, in contrast to the structures observed in solution. In the third case, (9-fluorenylmethoxycarbonyl (Fmoc)-Val-d-allo-Thr(ΨMe,Mepro)-OH), a cis-amide geometry is observed. These structural differences are attributed to crystal-packing interactions.

  核磁共振研究了 14 种源自苏氨酸的含假脯氨酸二肽（包括四种 d-allo-Thr 衍生物）的构象。在溶液中，所有二肽的主要构象都是假脯氨酸与前一个氨基酸之间的酰胺键为顺式。对于 N 端受到保护的二肽，顺式构象与反式构象的比例与 N 端氨基酸的侧链或 Thr 残基的立体化学关系不大。然而，对于具有自由 N 端的二肽，顺式转化物和反式转化物的比例因侧链的存在而存在显著差异。我们对三种二肽进行了结晶，并测定了它们的 X 射线结构。在两种情况下（苄氧羰基（Cbz）-Val-Thr(ΨMe,Mepro)-OMe 和 Cbz-Val-Thr(ΨMe,Mepro)-OH ），二肽在固态下采用了反式构象，这与在溶液中观察到的结构截然不同。在第三种情况（9-芴甲氧羰基（Fmoc）-Val-d-allo-Thr(ΨMe,Mepro)-OH）中，观察到的是顺式酰胺几何结构。这些结构差异归因于晶体-堆积相互作用。
• SORTASE A INHIBITORS
  申请人：Jung Michael E.

  公开号：US20120149710A1

  公开（公告）日：2012-06-14

  Bacterial infections, including Methicillin resistant Staphylococcus aureus (MRSA) infections are a major health problem that has created a pressing need for new antibiotics. Pyridazinone, rhodanine, and pyrazolethione compounds effective inhibit the enzymatic activity of sortase A (srtA) found in gram positive bacteria are disclosed. A structure activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC 50 values in the sub-micromolar range. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Many of these molecules also inhibit the sortase enzyme from B. anthracis suggesting that they may be generalized sortase inhibitors. The novel compounds, compositions, uses, formulations, medicaments, articles of manufacture provide improved materials, uses, and treatments useful in combating infectious disorders.

  细菌感染，包括甲氧西林耐药金黄色葡萄球菌（MRSA）感染，是一个重大的健康问题，已经创造了对新抗生素的迫切需求。本文披露了吡啶并咪唑酮、罗丹宁和吡唑硫酮化合物，这些化合物有效抑制了革兰氏阳性细菌中的srtA酶活性。结构活性关系（SAR）分析导致了多个吡啶并咪唑酮和吡唑硫酮类似物的鉴定，这些类似物以亚微摩尔范围内的IC50值抑制SrtA。抑制S. aureus SrtA酶的化合物可能作为强效抗感染剂，因为该酶将毒力因子附着在细胞壁上。其中许多分子也抑制了B. anthracis的sortase酶，表明它们可能是广谱的sortase抑制剂。这些新型化合物、组合物、用途、配方、药品和制造品提供了改进的材料、用途和治疗，对于抗击传染性疾病非常有用。
• Conversion of threonine derivatives to dehydroamino acids by elimination of .beta.-chloro and O-tosyl derivatives
  作者：Ananthachari Srinivasan、Robert W. Stephenson、Richard K. Olsen

  DOI：10.1021/jo00433a015

  日期：1977.6