(3-(benzyloxy)-4-methyl-2-nitrobenzoyl)-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone | 2478-48-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3-(benzyloxy)-4-methyl-2-nitrobenzoyl)-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone
• 英文别名: <3-(benzyloxy)-4-methyl-2-nitrobenzoyl>-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone；(3-(benzyloxy)-4-methyl-2-nitrobenzoyl)threonyl-D-valylprolylsarcosyl-N-methylvaline lactone；(3-benzyloxy-4-methyl-2-nitrobenzoyl)threonyl-D-valylprolylsarcosyl-N-methylvaline lactone；N-(3-benzyloxy-4-methyl-2-nitro-benzoyl)-L_s-threonyl->D-valyl->L-prolyl->N-methyl-glycyl->N-methyl-L-valine [1]3-lactone
• CAS: 2478-48-0
• 化学式: C₃₈H₅₀N₆O₁₀
• 分子量: 750.849
• InChiKey: ZWFUKFPSNOTIDR-WJGVMOIYSA-N

物化性质

• 沸点：
  978.7±65.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  54.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  197.8
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (3-(benzyloxy)-4-methyl-2-nitrobenzoyl)-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone 生成 更生霉素
  参考文献：
  名称：

  放线菌素，XXXV；合成放线菌素和放线菌素-染色体肽，VIII。Totalsynthese冯ANISO -Actinocinyl-peptiden UND ANISO -Actinomycinen尤伯杯氘markierte Vorstufen

  摘要：

  明镜Aufbau kurzkettiger ANISO -Actinocinyl-peptidester（16，19）UND放线菌素ähnlicher ANISO -Actinocinyl-pentapeptid-Paare wird beschrieben。Jeweils eines der zwei Stellungsisomeren或C-8 des Chromophors deuteriert；dadurch sind beide指出了NMR-spektroskopisch unterscheidbar和zuzuordnen。嗯…… B.死在α奥德βlactonisierten放线菌素c ^ 1 -säuren 34B UND 36B sowie ZWEI isomere ANISO -Actinocinyl肽MIT诺尔einem α-bzw. β-städidigen五肽内酰胺al

  DOI：

  10.1002/cber.19701030819
• 作为产物：
  描述：

  N-(3-(benzyloxy)-4-methyl-2-nitrobenzoyl)-O-(tert-butoxycarbonyl-N-methyl-L-valyl)-L-threonyl-D-valyl-L-prolylsarcosine ter-butyl ester 在 盐酸 、 sodium hydroxide 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 74.0h， 生成 (3-(benzyloxy)-4-methyl-2-nitrobenzoyl)-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone
  参考文献：
  名称：

  溶液和固态放线菌素相关肽内酯的构象和二聚化

  摘要：

  制备内酯 peptidiques 明显 a l'actinomycine et des actinomycinesrespondantes。Etude par RMN de 1 H des proprietes en solution de ces composes。结构结晶

  DOI：

  10.1021/ja00310a065

文献信息

• Studies on 2-Aziridinecarboxylic Acid. VIII. Total Synthesis of Actinomycin D and Its Serine Analogue<i>via</i>Ring-opening Reaction of 1-Benzyloxycarbonyl-2-aziridinecarboxylic Acid Moiety
  作者：Kiichiro Nakajima、Takumi Tanaka、Masahiro Neya、Kenji Okawa

  DOI：10.1246/bcsj.55.3237

  日期：1982.10

  Direct synthesis of peptides containing 1-benzyloxycarbonyl-2-aziridinecarboxylic acid were carried out by the reaction of β-hydroxy-α-amino acid peptides with DEAD–TPP reagents, and key O-peptide intermediates of actinomycin D synthesis were prepared via a ring-opening reaction of the aziridine with N-protected dipeptide. Peptide lactone was prepared by the DCC–HOBt method, and the subsequent debenzyl procedure and oxydation procedure gave the title compounds in good yields.

  通过β-羟基-α-氨基酸肽与DEAD-TPP试剂的反应，直接合成了含有1-苄氧羰基-2-氮丙啶羧酸的肽，并通过氮丙啶与N-保护二肽的开环反应，制备了放线菌素D合成的关键O肽中间体。用 DCC-HOBt 法制备了肽内酯，随后的去苄基程序和氧化程序以良好的收率得到了标题化合物。
• Toward the Design of an RNA:DNA Hybrid Binding Agent
  作者：Wenhua Chu、Shigehiro Kamitori、Miho Shinomiya、Robert G. Carlson、Fusao Takusagawa

  DOI：10.1021/ja00085a002

  日期：1994.3

  One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA: DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.