N-(N-tert-butoxycarbonyl-L-valyl)-N-methyl-L-leucine | 219813-88-4

• 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: N-(N-tert-butoxycarbonyl-L-valyl)-N-methyl-L-leucine
• 英文别名: N-Boc-L-Val-N-Me-L-Leu；Boc-Val-N(Me)Leu-OH；(2S)-4-methyl-2-[methyl-[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]pentanoic acid
• CAS: 219813-88-4
• 化学式: C₁₇H₃₂N₂O₅
• 分子量: 344.451
• InChiKey: UDAWCXNMNSPZIH-STQMWFEESA-N

物化性质

• 沸点：
  485.2±30.0 °C(Predicted)
• 密度：
  1.069±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(N-tert-butoxycarbonyl-L-valyl)-N-methyl-L-leucine 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 benzoic acid 4-{1-[2-methoxy-1-(1-{[1-(1-methoxycarbonyl-2,4-dimethyl-pent-3-enylcarbamoyl)-3-methyl-butyl]-methyl-carbamoyl}-2-methyl-propylcarbamoyl)-2-phenyl-ethylcarbamoyl]-ethylcarbamoyl}-2-methyl-4-methylamino-butyl ester
  参考文献：
  名称：

  Macrocyclization studies and total synthesis of cyclomarin C, an anti-inflammatory marine cyclopeptide

  摘要：

  The studies on macrocyclization at possible sites toward the total synthesis of cyclomarin C are described. The results showed that both Trp and Phe derivatives involved in the target could not be the terminals of the final linear peptide precursors. Additionally, preparation of corresponding dipeptides with an N-methyl amide bond is not favorable in the synthesis of linear precursors. Site d was finally proved a proper site for the cyclopeptide formation, and the corresponding head-to-tail macrocyclization was achieved under mild conditions and gave repeatable and satisfactory yields. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.03.058
• 作为产物：
  描述：

  N-甲基-L-亮氨酸 在 palladium on activated charcoal 氰基磷酸二乙酯 、 氢气 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 66.0h， 生成 N-(N-tert-butoxycarbonyl-L-valyl)-N-methyl-L-leucine
  参考文献：
  名称：

  Synthesis and Anti-Helicobacter pylori Activity of Pyloricidin Derivatives. I. Structure-activity Relationships on the Terminal Peptidic Moiety.

  摘要：

  新型天然抗生素喷菌素A、B和C对幽门螺杆菌具有强效且高度选择性的抗菌活性。为了研究末端肽部分的结构-活性关系，制备了一系列含不同氨基酸的喷菌素B和喷菌素C衍生物，并评估了它们的抗幽门螺杆菌活性。含有α-D-、β-和γ-氨基酸或肽模拟物的衍生物显示出显著降低的活性。另一方面，含有α-L-氨基酸的衍生物被发现能保持活性。在本工作中制备的衍生物中，烯丙基甘氨酸衍生物2s表现出最强的抗幽门螺杆菌活性，对幽门螺杆菌NCTC11637的最低抑制浓度（MIC）值小于0.006μg/ml，比原始化合物喷菌素C的活性高出60倍。

  DOI：

  10.7164/antibiotics.55.322

文献信息

• Isolation, Structure Elucidation and Total Synthesis of Lajollamide A from the Marine Fungus Asteromyces cruciatus
  作者：Tobias Gulder、Hanna Hong、Jhonny Correa、Ekaterina Egereva、Jutta Wiese、Johannes Imhoff、Harald Gross

  DOI：10.3390/md10122912

  日期：——

  The marine-derived filamentous fungus Asteromyces cruciatus 763, obtained off the coast of La Jolla, San Diego, USA, yielded the new pentapeptide lajollamide A (1), along with the known compounds regiolone (2), hyalodendrin (3), gliovictin (4), 1N-norgliovicitin (5), and bis-N-norgliovictin (6). The planar structure of lajollamide A (1) was determined by Nuclear Magnetic Resonance (NMR) spectroscopy in combination with mass spectrometry. The absolute configuration of lajollamide A (1) was unambiguously solved by total synthesis which provided three additional diastereomers of 1 and also revealed that an unexpected acid-mediated partial racemization (2:1) of the l-leucine and l-N-Me-leucine residues occurred during the chemical degradation process. The biological activities of the isolated metabolites, in particular their antimicrobial properties, were investigated in a series of assay systems.

  从美国圣地亚哥拉荷亚海岸获得的海洋来源丝状真菌Asteromyces cruciatus 763，产出了新的五肽lajollamide A (1)，以及已知化合物regiolone (2)、hyalodendrin (3)、gliovictin (4)、1N-norgliovicitin (5)和bis-N-norgliovictin (6)。lajollamide A (1)的平面结构通过核磁共振(NMR)光谱和质谱结合确定。lajollamide A (1)的绝对构型通过全合成得到明确解决，合成过程中获得了三个额外的非对映异构体，并揭示了在化学降解过程中l-亮氨酸和l-N-甲基亮氨酸残基发生了意外的酸介导部分消旋化(2:1)。对分离的代谢物的生物活性，特别是抗菌性质进行了系列检测。
• [EN] POLYOL-AMINO ACID COMPOUNDS HAVING ANTI-HELICOBACTER PYLORI ACTIVITY<br/>[FR] COMPOSES DE POLYOL ET D'ACIDES AMINES AGISSANT SUR L'HELICOBACTER PYLORI
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：WO1999002549A1

  公开（公告）日：1999-01-21

  (EN) A compound of formula (I) wherein R1 represents amino which may be substituted; R2 represents carboxy which may be esterified or amidated; R3, R4, R5, and R6 each represents hydroxy which may be protected; Q represents aryl which may be substituted; or a salt thereof. The compound (I) possesses anti-$i(Helicobacter pylori) activity, and useful in the prevention or treatment of various diseases associated with $i(Helicobacter) bacteria, such as duodenal ulcer, gastric ulcer, chronic gastritis, and cancer of the stomach.(FR) L'invention porte sur un composé de formule (I) dans laquelle R1 représente amino facultativement substitué; R2 représente carboxy facultativement estérifié ou amidé; R3, R4, R5 et R6 représentent chacun hydroxy facultativement protégé; Q représente aryle facultativement substitué; ou l'un de leurs sels. Le composé (I) agit sur l'$i(helicobacter pylori) et s'avère utile pour prévenir ou traiter différentes maladies associées à la bactérie $i(helicobacter) telles que l'ulcère duodénal, l'ulcère gastrique, les gastrites chroniques, et le cancer de l'estomac.

  化合物(I)的化学式为：其中R1代表可能被取代的氨基；R2代表可能被酯化或酰胺化的羧基；R3、R4、R5和R6各代表可能被保护的羟基；Q代表可能被取代的芳基；或其盐。该化合物(I)具有抗$ i(Helicobacter pylori)活性，并可用于预防或治疗与$ i(Helicobacter)细菌相关的各种疾病，如十二指肠溃疡、胃溃疡、慢性胃炎和胃癌。
• POLYOL-AMINO ACID COMPOUNDS HAVING ANTI-HELICOBACTER PYLORI ACTIVITY
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0998488A1

  公开（公告）日：2000-05-10
• US6423869B1
  申请人：——

  公开号：US6423869B1

  公开（公告）日：2002-07-23
• Synthesis and Anti-Helicobacter pylori Activity of Pyloricidin Derivatives. I. Structure-activity Relationships on the Terminal Peptidic Moiety.
  作者：ATSUSHI HASUOKA、YUJI NISHIKIMI、YUTAKA NAKAYAMA、KEIJI KAMIYAMA、MASAFUMI NAKAO、KEN-ICHIRO MIYAGAWA、OSAMU NISHIMURA、MASAHIKO FUJINO

  DOI：10.7164/antibiotics.55.322

  日期：——

  The novel natural antibiotics pyloricidin A, B and C possess potent and highly selective antibacterial activity against Helicobacter pylori. In order to investigate the structure activity relationships for the terminal peptidic moiety, a series of pyloricidin B and pyloricidin C derivatives, bearing various amino acids in the moiety, were prepared and evaluated for their anti-H. pylori activity. The derivatives bearing α-D-, β- and γ-amino acids or peptidemimetics showed drastically decreased activity. On the other hand, the derivatives with α-L-amino acids were found to maintain the activity. Among the derivatives prepared in this work, the allylglycine derivative 2s showed the most potent anti-H. pylori activity, with an MIC value of less than 0.006μg/ml against H. pylori NCTC11637, which is 60-fold greater than the activity of the lead compound pyloricidin C.

  新型天然抗生素喷菌素A、B和C对幽门螺杆菌具有强效且高度选择性的抗菌活性。为了研究末端肽部分的结构-活性关系，制备了一系列含不同氨基酸的喷菌素B和喷菌素C衍生物，并评估了它们的抗幽门螺杆菌活性。含有α-D-、β-和γ-氨基酸或肽模拟物的衍生物显示出显著降低的活性。另一方面，含有α-L-氨基酸的衍生物被发现能保持活性。在本工作中制备的衍生物中，烯丙基甘氨酸衍生物2s表现出最强的抗幽门螺杆菌活性，对幽门螺杆菌NCTC11637的最低抑制浓度（MIC）值小于0.006μg/ml，比原始化合物喷菌素C的活性高出60倍。