Z-N^βMe-L-A2Pr(Boc) | 130581-75-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Z-N^βMe-L-A2Pr(Boc)
• 英文别名: N^α-(benzyloxycarbonyl)-N^β-(tert-butoxycarbonyl)-N^β-methyl-L-α,β-diaminopropionic acid；(2S)-3-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 130581-75-8
• 化学式: C₁₇H₂₄N₂O₆
• 分子量: 352.387
• InChiKey: MDYCNFWIIRRPEI-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.23
• 重原子数：
  25.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  105.17
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  Z-N^βMe-L-A2Pr(Boc) 在 palladium on activated charcoal 氰基磷酸二乙酯 、 二苯基膦叠氮化物 、 氢气 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.0h， 生成 tert-butyl N-[4-[[2-[[(2S)-2-[[(3R)-4-[(4S,5S)-5-amino-2,2-dimethyl-1,3-dioxan-4-yl]-3-hydroxybutanoyl]amino]-3-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoyl]amino]acetyl]amino]butyl]-N-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]carbamate
  参考文献：
  名称：

  加兰汀的全合成I.原始结构的修订

  摘要：

  提出的加兰汀I的建议结构（作为同系物的混合物（1a / 1b = 9/1）分离）在总合成中显示是不正确的，并且经过两次修订以最终在总合成中分别得到5a和5c。

  DOI：

  10.1016/s0040-4039(00)94727-0
• 作为产物：
  描述：

  (S)-2-N-Cbz-3-N-Boc-丙酸甲酯 在 三乙基硅烷 、 sodium hydroxide 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 31.33h， 生成 Z-N^βMe-L-A2Pr(Boc)
  参考文献：
  名称：

  Total synthesis of galantin I. Acid-catalyzed cyclization of galantinic acid

  摘要：

  The proposed structure of galantin 1, a peptide antibiotic isolated from Bacillus pulvifaciens as a mixture of congeners (1a with the D-ornithine residue and lb with D-lysine; 1a/1b = 9/1), was shown to be incorrect by total synthesis. The substructure 3a, named galantinic acid, was an artifact, and its correct structure was assumed to be the hydroxylated form, 20a or 20b, by spectroscopic comparisons of synthetic la with natural galantin I. The synthesis of both diastereomers, 4a and 4b, again suggested that the sequence of the spermidine moiety of galantin I should be N5,N8. Finally, the correct structure of galantin I as 5a was confirmed by the synthesis of diastereomers 5a and 5b. The synthesis of 5a was accomplished in a convergent manner by the coupling of the protected forms of the constituent amino acids: D-ornithine, 6b, D-alanine, 23b, 11b, 8c, and 19a. Galantinic acid residue 20a, present in natural galantin 1, was found to undergo cyclization with retention of its C3 configuration under the chemical degradation conditions to give the artifact 3a. In order to elucidate the mode of cyclization of 20a to 3a, the synthesis of 20a and its analogues was accomplished in a stereoselective manner from D-serine. The synthesis was characterized by the stereoselective epoxidation of hydroxymethyl (Z)-allylamine 34 and alpha,beta-unsaturated delta-lactone 39. Acidolysis of 20a, 20b, and their analogues suggested that the stereoselective cyclization of galantinic acid was initiated by the formation of delta-lactone 54, which through the sequence of reactions should afford the artifact 3a.

  DOI：

  10.1021/ja00029a031

文献信息

• MACROCYCLIC ANTAGONISTS OF THE MOTILIN RECEPTOR FOR TREATMENT OF GASTROINTESTINAL DYSMOTILITY DISORDERS
  申请人：Marsault Eric

  公开号：US20100093720A1

  公开（公告）日：2010-04-15

  The present invention provides conformationally-defined macrocyclic compounds that bind to and/or are functional modulators of the motilin receptor including subtypes, isoforms and/or variants thereof. These macrocyclic compounds, at a minimum, possess adequate pharmacological properties to be useful as therapeutics for a range of disease indications. In particular, these compounds are useful for treatment and prevention of disorders characterized by hypermotilinemia and/or gastrointestinal hypermotility, including, but not limited to, diarrhea, cancer treatment-related diarrhea, cancer-induced diarrhea, chemotherapy-induced diarrhea, radiation enteritis, radiation-induced diarrhea, stress-induced diarrhea, chronic diarrhea, AIDS-related diarrhea, C. difficile associated diarrhea, traveller's diarrhea, diarrhea induced by graph versus host disease, other types of diarrhea, dyspepsia, irritable bowel syndrome, chemotherapy-induced nausea and vomiting (emesis) and post-operative nausea and vomiting and functional gastrointestinal disorders. In addition, the compounds possess utility for the treatment of diseases and disorders characterized by poor stomach or intestinal absorption, such as short bowel syndrome, celiac disease and cachexia. The compounds also have use for the treatment of inflammatory diseases and disorders of the gastrointestinal tract, such as inflammatory bowel disease, ulcerative colitis, Crohn's disease and pancreatitis. Accordingly, methods of treating such disorders and pharmaceutical compositions including compounds of the present invention are also provided.

  本发明提供了与胃动素受体及其亚型、异构体和/或变体结合和/或是功能调节剂的构象定义明确的大环化合物。这些大环化合物至少具有足够的药理特性，可用作治疗一系列疾病指示的治疗药物。特别是，这些化合物对于治疗和预防以高胃动素血症和/或胃肠道高蠕动性为特征的疾病非常有用，包括但不限于腹泻、癌症治疗相关腹泻、癌症诱导腹泻、化疗诱导腹泻、放射性肠炎、放射性腹泻、压力诱导腹泻、慢性腹泻、艾滋病相关腹泻、C. difficile相关腹泻、旅行者腹泻、移植物宿主病引起的腹泻、其他类型的腹泻、消化不良、肠易激综合征、化疗诱导的恶心和呕吐（呕吐）以及术后恶心和呕吐和功能性胃肠道疾病。此外，这些化合物对于治疗以胃或肠道吸收不良为特征的疾病和疾病也具有用途，例如短肠综合征、乳糜泻和虚弱。这些化合物还可用于治疗胃肠道炎症性疾病和疾病，如炎症性肠病、溃疡性结肠炎、克罗恩病和胰腺炎。因此，本发明还提供了治疗此类疾病的方法和包括本发明化合物的药物组合物。
• Total Synthesis and Biological Evaluation of Paenilamicins from the Honey Bee Pathogen <i>Paenibacillus larvae</i>
  作者：Timur Bulatov、Sebastian Gensel、Andi Mainz、Tam Dang、Timm O. Koller、Kerstin Voigt、Julia Ebeling、Daniel N. Wilson、Elke Genersch、Roderich D. Süssmuth

  DOI：10.1021/jacs.1c09616

  日期：2022.1.12

  Paenibacillus larvae causing the lethal brood disease American Foulbrood (AFB). Here, we report the convergent total synthesis and structural revision of paenilamicin B2. Specific stereoisomers of paenilamicin B2 were synthesized for unambiguous confirmation of the natural product structure and for evaluation of biological activities. These studies revealed the N-terminal fragment of paenilamicin as an important

  类青霉素是一组复杂的聚阳离子肽次级代谢产物，具有抗菌和抗真菌活性，由破坏性蜜蜂幼虫病原体类芽孢杆菌幼虫产生，引起致命的幼虫病美洲臭虫病 (AFB)。在此，我们报道了青霉素B2的收敛全合成和结构修正。合成了青霉素 B2 的特定立体异构体，以明确确认天然产物结构并评估生物活性。这些研究揭示了青霉素的 N 末端片段是一种重要的药效基团。使用蜜蜂幼虫和昆虫病原体苏云金芽孢杆菌进行的感染试验表明，青霉霉素在蜜蜂幼虫生态位中击败了细菌竞争对手。最后，我们展示了将青霉素分类为潜在核糖体抑制剂的第一个数据。因此，我们的合成路线是了解P. larvae致病性以及在不久的将来进行彻底的结构-活性-关系以及作用模式研究的又一步。
• Design and Application of Basic Amino Acids Displaying Enhanced Hydrophobicity
  作者：Juliana K. Kretsinger、Joel P. Schneider

  DOI：10.1021/ja029892o

  日期：2003.7.1

  interfacial spaces of proteins. As a demonstration of their utility, the ability of these residues to promote interior salt bridge formation at the helix/helix interface of GCN4-p1, a dimeric two-stranded coiled coil, was assessed. Heterodimerization mediated by buried salt bridge formation between a GCN4-based peptide containing either mmdap, dmdap, or tmdap at position 16 and an analogous peptide

  已经合成了三种非编码碱性氨基酸，单-、二-和三甲基二氨基丙酸（mmdap、dmdap 和 tmdap），用于蛋白质设计。具有增加的甲基部分的二氨基丙酸 (dap) 侧链的共价修饰导致一系列残基显示出具有不同程度增强的疏水特性的短碱性侧链。这些残基可用于将带电/极性相互作用引入蛋白质的限制性疏水内部或界面空间。作为其效用的证明，评估了这些残基促进 GCN4-p1（一种二聚体双链卷曲螺旋）的螺旋/螺旋界面处内部盐桥形成的能力。由含 mmdap、dmdap 或 dmdap 的基于 GCN4 的肽之间的埋盐桥形成介导的异二聚化 或 tmdap 在第 16 位，并研究了在相同位置含有天冬氨酸的类似肽。Mmdap 衍生的异二聚体比相应的 dap 衍生的异二聚体稳定 0.5 kcal/mol。这一结果表明向 dap 侧链添加一个甲基可以稳定异二聚体折叠。稳定化最有可能归因于折叠时发生的去溶剂化惩罚的减少
• Consequences of Depsipeptide Substitution on the ClpP Activation Activity of Antibacterial Acyldepsipeptides
  作者：Yangxiong Li、Nathan P. Lavey、Jesse A. Coker、Jessica E. Knobbe、Dat C. Truong、Hongtao Yu、Yu-Shan Lin、Susan L. Nimmo、Adam S. Duerfeldt

  DOI：10.1021/acsmedchemlett.7b00320

  日期：2017.11.9

  The acyldepsipeptide (ADEP) antibiotics operate through a clinically unexploited mechanism of action and thus have attracted attention from several antibacterial development groups. The ADEP scaffold is synthetically tractable, and deep-seated modifications have produced extremely potent antibacterial leads against Gram-positive pathogens. Although newly identified ADEP analogs demonstrate remarkable antibacterial activity against bacterial isolates and in mouse models of bacterial infections, stability issues pertaining to the depsipeptide core remain. To date, no study has been reported on the natural ADEP scaffold that evaluates the sole importance of the macrocyclic linkage on target engagement, molecular conformation, and bioactivity. To address this gap in ADEP structure-activity relationships, we synthesized three ADEP analogs that only differ in the linkage motif (i.e., ester, amide, and N-methyl amide) and provide a side-by-side comparison of conformational behavior and biological activity. We demonstrate that while replacement of the naturally occurring ester linkage with a secondary amide maintains in vitro biochemical activity, this simple substitution results in a significant drop in whole-cell activity. This study provides direct evidence that ester to amide linkage substitution solution for ADEP instability.
• SAKAI, NAOMI;OHFUNE, YASUFUMI, TETRAHEDRON LETT., 31,(1990) N2, C. 3183-3186
  作者：SAKAI, NAOMI、OHFUNE, YASUFUMI

  DOI：——

  日期：——