(R)-1-tert-butyl 5-methyl 2-aminopentanedioate | 23577-91-5

• 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: (R)-1-tert-butyl 5-methyl 2-aminopentanedioate
• 英文别名: (R)-1-tert-Butyl5-methyl2-aminopentanedioate；1-O-tert-butyl 5-O-methyl (2R)-2-aminopentanedioate
• CAS: 23577-91-5
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: QSAXGMMUKHMOBI-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-1-tert-butyl 5-methyl 2-aminopentanedioate 在 水 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (R)-5-(tert-butoxy)-4-(18-(tert-butoxy)-18-oxooctadecanamido)-5-oxopentanoic acid
  参考文献：
  名称：

  [EN] PCSK9 ANTAGONIST COMPOUNDS
  [FR] COMPOSÉS ANTAGONISTES DU PCSK

  摘要：

  揭示了化合物的结构式（I），或其药用盐：（I）其中A，A1，A2，R1，R2和R3如本文所定义，这些化合物具有拮抗PCSK9的属性。还描述了包含结构式I的化合物或其盐的制药配方，以及治疗心血管疾病和与PCSK9活性相关的疾病的方法，例如动脉粥样硬化，高胆固醇血症，冠心病，代谢综合征，急性冠状综合征或相关心血管疾病和心脏代谢疾病的条件。

  公开号：

  WO2021127460A1
• 作为产物：
  描述：

  α-tert-butyl γ-methyl N-(benzyloxycarbonyl)-D-glutamate 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 生成 (R)-1-tert-butyl 5-methyl 2-aminopentanedioate
  参考文献：
  名称：

  A new synthesis of poly-γ-D- and L-glutamic acid

  摘要：

  通过γ-谷氨酰谷氨酰酸-α,α'-二叔丁基-γ-五氯苯酰酯的缩聚，描述了一种新的合成天然多谷氨酸的方法。这种途径消除了转肽作用的可能性。

  DOI：

  10.1139/v69-609

文献信息

• Enantioselective synthesis of α-benzylated lanthionines and related tripeptides for biological incorporation into E. coli peptidoglycan
  作者：Thibaut Denoël、Astrid Zervosen、Christian Lemaire、Bernard Joris、Mireille Hervé、Didier Blanot、Guillermo Zaragoza、André Luxen

  DOI：10.1039/c4ob01476f

  日期：——

  The synthesis of modified tripeptides (S)-Ala-γ-(R)-Glu-X, where X = (R,S) or (R,R) diastereomers of α-benzyl or α-(4-azidobenzyl)lanthionine, was carried out. The chemical strategy involved the enantioselective alkylation of a 4-MeO-phenyloxazoline. The reductive opening of the alkylated oxazolines, followed by cyclization and oxidation, led to four PMB-protected sulfamidates. Subsequent PMB removal, Boc protection and regioselective opening with cysteine methyl ester led to protected lanthionines. These compounds were further converted in a one pot process to the corresponding protected tripeptides. After ester and Boc deprotection, the four tripeptides were evaluated as potential analogues of the natural tripeptide (S)-Ala-γ-(R)-Glu-meso-A2pm. These compounds were evaluated for introduction, by means of the biosynthetic recycling pathway, into the peptidoglycan of Escherichia coli. A successful in vitro biosynthesis of UDP-MurNAc-tripeptides from the tripeptides containing α-benzyl lanthionine was achieved using purified murein peptide ligase (Mpl). Bioincorporation into E. coli W7 did not occur under different tested conditions probably due to the bulky benzyl group at the Cα carbon of the C-terminal amino acid.

  我们合成了修饰三肽 (S)-Ala-δ-(R)-Glu-X，其中 X = δ-苄基或δ-(4-叠氮基苄基)兰硫鎓的(R,S)或(R,R)非对映异构体。化学策略涉及 4-MeO-苯基噁唑啉的对映选择性烷基化。烷基化的噁唑啉还原开放，然后进行环化和氧化，最终得到四个 PMB 保护的氨基磺酸盐。随后通过去除 PMB、Boc 保护和半胱氨酸甲酯的区域选择性开环，得到了受保护的镧系元素。这些化合物通过一锅法进一步转化为相应的受保护三肽。经过酯和 Boc 去保护后，这四种三肽被评估为天然三肽 (S)-Ala-γ-(R)-Glu-meso-A2PM 的潜在类似物。对这些化合物进行了评估，以便通过生物合成循环途径将其引入大肠杆菌的肽聚糖中。利用纯化的金霉素肽连接酶（Mpl），成功地从含有δ-苄基兰硫氨酸的三肽体外生物合成了 UDP-MurNAc-三肽。在不同的测试条件下，大肠杆菌 W7 都没有发生生物卟啉化，这可能是由于 C 端氨基酸 Cδ 碳上的苄基过大所致。
• Highly enantioselective synthesis of cyclic and functionalized α-amino acids by means of a chiral phase transfer catalyst
  作者：E.J Corey、Mark C Noe、Feng Xu

  DOI：10.1016/s0040-4039(98)01067-3

  日期：1998.7

  The chiral quaternary ammonium salt 1 serves as phase transfer catalyst for the enantioselective conversion of the glycine derivative 2 to a variety of cyclic and acyclic chiral α-amino acids with enantioselectivities as high as 200:1 in alkylation and Michael addition reactions.

  手性季铵盐1充当相转移催化剂，用于在烷基化和迈克尔加成反应中将甘氨酸衍生物2对映选择性转化为对映选择性高达200：1的各种环状和无环手性α-氨基酸。
• AMINOBUTANOIC ACID DERIVATIVES
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1024134A1

  公开（公告）日：2000-08-02

  An aminobutyric acid derivative of the formula (I): (wherein all symbols are as defined in the specification) and salt thereof. salt thereof. The compounds of the formula (I) possess an inhibitory activity on matrix metalloproteinase and are useful for prevention and / or treatment of diseases, for example, rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion of or growth of tumor cells, autoimmune disease (e.g. Crohn's disease, Sjogren's syndrome), disease caused by vascular emigration or infiltration of leukocytes, arterialization, multiple sclerosis, aorta aneurysm, endometriosis.

  式（I）的氨基丁酸衍生物： (其中所有符号如说明书中所定义）及其盐。 式（I）化合物对基质金属蛋白酶具有抑制活性，可用于预防和/或治疗疾病，例如类风湿病、关节炎、异常骨吸收、骨质疏松症、牙周炎、间质性肾炎、动脉硬化、肺气肿、肝硬化、角膜损伤、肿瘤细胞的转移、侵入或生长、自身免疫性疾病（如克罗恩病、Sj.如克罗恩病、Sjogren 综合症）、血管移位或白细胞浸润引起的疾病、动脉化、多发性硬化、主动脉瘤、子宫内膜异位症。
• Design, Synthesis, and Evaluation of Benzothiadiazepine Hydroxamates as Selective Tumor Necrosis Factor-α Converting Enzyme Inhibitors
  作者：Robert J. Cherney、James J.-W. Duan、Matthew E. Voss、Lihua Chen、Li Wang、Dayton T. Meyer、Zelda R. Wasserman、Karl D. Hardman、Rui-Qin Liu、Maryanne B. Covington、Mingxin Qian、Sandhya Mandlekar、David D. Christ、James M. Trzaskos、Robert C. Newton、Ronald L. Magolda、Ruth R. Wexler、Carl P. Decicco

  DOI：10.1021/jm020475w

  日期：2003.5.1

  Elevated levels of tumor necrosis factor-alpha (TNF-alpha) have been associated with several inflammatory diseases, and therefore, strategies for its suppression have become important targets in drug discovery. Our efforts to suppress TNF-alpha have centered on the inhibition of TNF-alpha converting enzyme (TACE) through the use of hydroxamate inhibitors. Starting from broad-spectrum matrix metalloproteinase (MMP) inhibitors, we have designed and synthesized novel benzothiadiazepines as potent and selective TACE inhibitors. The benzothiadiazepines were synthesized with variation in P1 and P1' in order to effect potency and selectivity. The inhibitors were evaluated versus porcine TACE (pTACE), and the initial selectivity was assessed with counterscreens of MMP-1, -2, and -9. Several potent and selective inhibitors were discovered with compound 41 being the most active against pTACE (K-i = 5 nM) while still maintaining good selectivity versus the MMP's (at least 75-fold). Most compounds were assessed in the human peripheral blood mononuclear cell assay (PBMC) and the human whole blood assay (WBA) to determine their ability to suppress TNF-alpha. Compound 32 was the most potent compound in the PBMC assay (IC50 = 0.35 muM), while compound 62 was the most active in the WBA (IC50 = 1.4 muM).
• NOVEL CYCLIC SULFONAMIDE DERIVATIVES AS METALLOPROTEINASE INHIBITORS
  申请人：Du Pont Pharmaceuticals Company

  公开号：EP1054877A1

  公开（公告）日：2000-11-29