Boc-Ala-Leu-OBn | 56618-30-5

• 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: Boc-Ala-Leu-OBn
• 英文别名: N-(tert-butoxycarbonyl)-L-alanyl-L-leucine benzyl ester；Boc-Ala-Leu-OBzl；N-tert-butoxycarbonylalanylleucine benzyl ester；benzyl (2S)-4-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]pentanoate
• CAS: 56618-30-5
• 化学式: C₂₁H₃₂N₂O₅
• 分子量: 392.495
• InChiKey: ITIDKGWTBMJWPL-RDJZCZTQSA-N

物化性质

• 沸点：
  537.8±35.0 °C(Predicted)
• 密度：
  1.091±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-Ala-Leu-OBn 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 氢气 、 氯甲酸异丁酯 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 36.17h， 生成 N-(tert-butoxycarbonyl)-valyl-alanyl-leucine
  参考文献：
  名称：

  C-Alkylation of Peptides Containing Aminomalonate and (Amino)(cyano)acetate Residues

  摘要：

  N-Acetyl-, N-[(tert-butoxy)carbonyl](Boc)-, and N-[(benzyloxy)carbonyl](Z)-protected tri-, penta-, and heptapeptide methyl esters, 1-8, with a central aminomalonate (Ama) (allyl, methyl, benzyl, or tert-butyl) or (amino)(cyano)acetate (Aca) residue have been prepared by conventional techniques (Schemes 4-6). The new peptides with acidic backbone-bound CH groups can be C-alkylated with primary alkyl, allyl, and benzyl halides, under mildly basic conditions (1 equiv. MeONa or t-BuOK in THF); also, they can be added to Michael accepters such as acrylates, acrylonitrile, methyl vinyl ketone, or nitrostyrene (catalytic amounts of alkoxide bases in THF) (Schemes 7-16). In most cases, the products, 48-100, are formed in excellent yields (average of 77%); one of the epimeric products prevails (2:1 to > 20:1), and the epimers have been separated, isolated in pure form, and fully characterized (without configurational assignments); addition of the co-solvent 3,4,5,6-tetrahydro-1,3-dimethylpyrimidin-2(1H)-one (DMPU) or of LiBr may improve or even reverse the ratio of epimeric products formed; the heptapeptide derivative 8 had to be solubilized for alkylations in THF by the addition of 30 equiv. of LiBr. Cleavage of the Ama groups (benzyl with H-2/Pd-C, t-Bu with HCl/Et2O) gave carboxylate derivatives which are actually peptides containing the alkylated aminomalonic acid, the lower homolog of aspartic acid, as residue in the central position. These acids are quite resistant to decarboxylation which had to be achieved by heating at reflux in THF in the presence of 2 equiv. of LiBr and of catalytic amounts of pyridine (Schemes 17 and 18). A one-step removal of the allyl aminomalonate group is possible with Pd/PPh3/formate (Scheme 19). The resulting peptides, 101-115, were formed as separable I: 1 mixtures of two epimers. The CN group of the alkylated Aca residue can be removed reductively (Na/NH3; Scheme 20). The value of the new method is compared with that of existing methods of peptide-backbone modification.

  DOI：

  10.1002/(sici)1522-2675(19981007)81:10<1845::aid-hlca1845>3.0.co;2-l
• 作为产物：
  描述：

  L-亮氨酸苄酯对甲苯磺酸盐 、 Boc-L-丙氨酸 N-丁二酰亚胺酯 在 N-甲基吗啉 作用下， 生成 Boc-Ala-Leu-OBn
  参考文献：
  名称：

  Chemical modification of peptides containing .gamma.-carboxyglutamic acid

  摘要：

  DOI：

  10.1021/jo00349a003

文献信息

• Biodegradable Microspheres. 16. Synthesis of Primaquine–Peptide Spacers for Lysosomal Release from Starch Microparticles
  作者：Rossitsa Borissova、Bernard Lammek、Peter Stjärnkvist、Ingvar Sjöholm

  DOI：10.1002/jps.2600840226

  日期：1995.2

  tetrapeptide spacer arm for the rate of lysosomal enzymatic release of PQ can be possible. A third group, comprising epsilon-aminocaproic acid-PQ derivatives which lack a free alpha-amino group, was synthesized. This was done to study the importance of enzymes, other than aminopeptidases, during lysosomal degradation of these derivatives. To allow HPLC analysis of the pattern of degradation of tetrapeptide-PQ

  采用经典的肽合成方法合成了四组化合物，并为每组化合物开发了分析方法。其中两个是抗衰老药物伯氨喹（PQ）的四肽衍生物，其一般结构为NH2-X-Leu-Ala-Y-PQ。第一组，Y位置使用Leu，Tyr，Lys和Asp，而X为Ala；第二组，X位置使用Ala，Tyr，Lys和Asp在X位置，Y为Leu。这些衍生物旨在通过其游离的α-氨基与聚丙烯酸酯淀粉微粒（在我们实验室开发的溶同溶性药物载体）偶联。因此，对PQ的溶酶体酶促释放速率的四肽间隔臂的不同氨基酸组成的重要性的系统研究是可能的。第三组 合成了包含缺少游离α-氨基的ε-氨基己酸-PQ衍生物的化合物。这样做是为了研究在这些衍生物的溶酶体降解过程中除氨肽酶以外的酶的重要性。为了允许HPLC分析四肽-PQ衍生物的降解模式，还制备了一些较短的肽-PQ衍生物（第四组）。
• Photocatalytic Activation of Elemental Sulfur Enables a Chemoselective Three-Component Thioesterification
  作者：Sho Murakami、Takeshi Nanjo、Yoshiji Takemoto

  DOI：10.1021/acs.orglett.1c02904

  日期：2021.10.1

  thioesterification using olefins, α-ketoacids, and elemental sulfur has been developed. The photocatalytic activation of elemental sulfur, a cheap and abundant sulfur source, enables the rapid installation of a sulfur atom into molecules, reactions that ordinarily would require the use of reactive and malodorous sulfur-containing compounds such as thiols and thioacids. This novel reaction is characterized

  已经开发出使用烯烃、α-酮酸和元素硫的温和且化学选择性的三组分硫酯化反应。元素硫的光催化活化是一种廉价且丰富的硫源，能够将硫原子快速安装到分子中，而这些反应通常需要使用反应性和恶臭的含硫化合物，如硫醇和硫代酸。这种新反应的特点是产量高，底物范围广，可以将硫酯部分引入复杂的分子中，包括类固醇、肽和未受保护的糖苷。机理研究表明，这种转变的成功取决于元素硫所发挥的多种作用，包括硫化剂、末端氧化剂和 HAT 介质。
• Cyclic Peptidic Mimetics of Apollo Peptides Targeting Telomeric Repeat Binding Factor 2 (TRF2) and Apollo Interaction
  作者：Xia Chen、Liu Liu、Yong Chen、Yuting Yang、Chao-Yie Yang、Tianyue Guo、Ming Lei、Haiying Sun、Shaomeng Wang

  DOI：10.1021/acsmedchemlett.8b00152

  日期：2018.5.10

  TRF2. In this Letter, we report the design and synthesis of a class of cyclic peptidic mimetics of the TRFH binding motif of Apollo (ApolloTBM). We found conformational control of the C terminal residues of ApolloTBM can effectively improve the binding affinity. We have obtained a crystal structure of a cyclic peptidic Apollo peptide mimetic (34) complexed with TRF2, which provides valuable guidance to

  端粒重复结合因子2（TRF2）是一种端粒相关蛋白，在3'单链DNA突出端和“ T环”（端粒稳定性至关重要的两个结构）的形成中起着重要作用。阿波罗是由TRF2募集到端粒的5'核酸外切酶，并有助于3'单链DNA突出端的形成。敲除阿波罗可以诱导类似于TRF2敲除引起的DNA损伤反应。在这封信中，我们报告了阿波罗TRFH结合基序（Apollo TBM）的一类环状肽模拟物的设计和合成。我们发现阿波罗TBM C末端残基的构象控制可以有效提高结合亲和力。我们已经获得了与TRF2络合的环状肽Apollo肽模拟物（34）的晶体结构，这为TRF2抑制剂的未来设计提供了有价值的指导。
• Peptide carbazates and pharmaceutical composition
  申请人：Merck & Co., Inc.

  公开号：US04064236A1

  公开（公告）日：1977-12-20

  Certain novel peptide carbazates, their preparation, pharmaceutical compositions and novel methods of treating pancreatitis.

  某些新型肽类卡巴曲酰胺、它们的制备、制药组合物和治疗胰腺炎的新方法。
• KETOAMIDE IMMUNOPROTEASOME INHIBITORS
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20150274777A1

  公开（公告）日：2015-10-01

  The invention is concerned with the compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein X, R 1 , R 1′ , R 2 , R 2′ , R 3 , R 4 , R 4′ and R 5 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are LMP7 inhibitors and may be useful in treating associated inflammatory diseases and disorders such as, for example, rheumatoid arthritis, lupus and irritable bowel disease.

  本发明涉及式(I)的化合物及其药学上可接受的盐，其中X、R1、R1'、R2、R2'、R3、R4、R4'和R5在详细说明书和权利要求中有定义。此外，本发明还涉及制造和使用式(I)化合物的方法，以及含有这种化合物的药物组合物。式(I)化合物是LMP7抑制剂，可能有用于治疗相关的炎症性疾病和疾病，例如类风湿性关节炎、狼疮和肠易激综合症。