(2S,3R)-2-((tert-butoxycarbonyl)(methyl)amino)-3-methoxybutanoic acid | 136092-75-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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: (2S,3R)-2-((tert-butoxycarbonyl)(methyl)amino)-3-methoxybutanoic acid
• 英文别名: N-(tert-butoxycarbonyl)-n,o-dimethyl-l-threonine；(2S,3R)-3-methoxy-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoic acid
• CAS: 136092-75-6
• 化学式: C₁₁H₂₁NO₅
• 分子量: 247.291
• InChiKey: GPOFBERDSRBKHN-SFYZADRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R)-2-((tert-butoxycarbonyl)(methyl)amino)-3-methoxybutanoic acid 在 盐酸 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 (2S,3R)-N,O-Me2Thr
  参考文献：
  名称：

  Structure of YM-254890, a Novel Gq/11 Inhibitor from Chromobacterium sp. QS3666

  摘要：

  The isolation and structure elucidation of YM-254890, a novel G(q/11) inhibitor from Chromobacterium sp. QS3666, is described. The gross structure was determined by one- and two-dimensional NMR studies and mass spectrometry. YM-254890 is a cyclic depsipeptide containing uncommon amino acids; beta-hydroxyleucine (two residues), N,O-dimethylthreonine and N-methyldehydroalanine. YM-254890 exists as a mixture of two conformers in a variety of NMR solvents, and the distinction between major and minor conformers appears to lie in the geometry of the amide bond between 3-phenyllactic acid and N-methyldehydroalanine. The absolute stereochemistery was elucidated by Mar-fey's analysis and chiral HPLC analysis of the acid hydrolysate of YM-254890. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(03)00680-x
• 作为产物：
  描述：

  在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 以100 %的产率得到(2S,3R)-2-((tert-butoxycarbonyl)(methyl)amino)-3-methoxybutanoic acid
  参考文献：
  名称：

  YM-385781 全合成的构建模块方法

  摘要：

  已开发出合成 YM 和 FR 类似物的构建模块方法，并将其用于 YM-385781 的合成。最终类似物的结构通过光谱和生物测定得到证实，有趣的是，即使是这里制造的效力较低的合成类似物也能够抑制致癌的 Gq 信号传导和葡萄膜黑色素瘤细胞的生长。

  DOI：

  10.1002/ejoc.202300365

文献信息

• Total Synthesis of the Cyclic Depsipeptide YM-280193, a Platelet Aggregation Inhibitor
  作者：Harveen Kaur、Paul W. R. Harris、Peter J. Little、Margaret A. Brimble

  DOI：10.1021/ol503507g

  日期：2015.2.6

  first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the ADP-induced aggregation of human platelets, is described. The monomer and dipeptide fragments were prepared using conventional chemistry and subsequently assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel bis-alkylation–elimination of cysteine on-resin was employed to introduce the unnatural N-methyldehydroalanine

  描述了YM-280193的第一个全合成，这是一种环状的二肽，可抑制ADP诱导的人血小板聚集。使用常规化学方法制备单体和二肽片段，然后通过Fmoc-固相肽合成（Fmoc-SPPS）进行组装。一种新型的半烷基树脂上的双烷基化消除后期方法被用来引入非天然的N-甲基脱氢丙氨酸部分。最后一步涉及在受阻碍的非天然N，O-二甲基苏氨酸和β-羟基亮氨酸残基之间进行关键的大内酰胺化反应。
• Synthesis of new indolactam analogues by microbial conversion
  作者：Shin-ichiro Kajiyama、Kazuhiro lrie、Takae Kido、Koichi Koshimizu、Hideo Hayashi、Motoo Arai

  DOI：10.1016/s0040-4020(01)80978-9

  日期：1991.7

  Abu, γ,δ-Δ-Nva, Nva, Nle, tert-Leu, Leu, Ile, allo-Ile. Phg instead ofL-Val in (−)-indolactam-Val, were synthesized from their seco-compounds (N-methyl-L-amino acidyl-L-tryptophonol) by microbial conversion.

  与L-Ala，Abu，γ，δ-Δ-Nva，Nva，Nle，ter-Leu，Leu，Ile，allo-Ile的十个吲哚内酰胺同类物。通过微生物转化，由它们的山高化合物（N-甲基-L-氨基酸基-L-色酚）合成了Phg而不是（-）-吲哚内酰胺-Val中的L-Val。
• Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates
  作者：Kondaparla Srinivasarao、Pooja Agarwal、Kumkum Srivastava、W. Haq、Sunil K. Puri、S. B. Katti

  DOI：10.1007/s00044-016-1555-5

  日期：2016.6

  screened for in vitro antiplasmodial activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Among the series, compounds 30 and 31 showed significant inhibition of parasite growth against K1 strain of P. falciparum with IC50 values 0.28 and 0.31 µM, respectively, whereas compounds 34, 35, and 38 exhibited superior activity against K1 strain

  摘要合成了一系列新的侧链修饰的4-氨基喹啉，并筛选了针对恶性疟原虫的氯喹敏感（3D7）和耐氯喹（K1）菌株的体外抗血浆活性。间的系列中，化合物30和31表现出对的K1株寄生虫生长的抑制显著恶性疟原虫与IC 50个值0.28和0.31μM，分别，而化合物34，35，和38显示出优异的活性针对K1菌株的IC 50值分别为0.18、0.22和0.17 µM，而氯喹（CQ）的值为0.255 µM。所有化合物在1.54至> 34.48之间均显示出良好的抗性因子，而CQ为51.0。发现所有这些类似物均与血红素形成强复合物，并在体外抑制β-血红素的形成，表明这类化合物可作用于血红素聚合目标。总体结果表明，本系列化合物似乎有望用于进一步的铅优化以获得对耐药性寄生虫具有活性的化合物。 图形概要
• Structure–activity relationship and conformational studies of the natural product cyclic depsipeptides YM-254890 and FR900359
  作者：Hang Zhang、Alexander L. Nielsen、Michael W. Boesgaard、Kasper Harpsøe、Norelle L. Daly、Xiao-Feng Xiong、Christina R. Underwood、Linda M. Haugaard-Kedström、Hans Bräuner-Osborne、David E. Gloriam、Kristian Strømgaard

  DOI：10.1016/j.ejmech.2018.07.023

  日期：2018.8

  G proteins are key mediators in the signaling of G protein-coupled receptors and involved in a plethora of important physiological processes. The natural product cyclic depsipeptides YM-254890 and FR900359 are the only known selective inhibitors of the G(q) protein subfamily. So far, all reported YM-254890 and FR900359 analogs show no inhibition of other G protein subtypes except the G(q), G(11) and G(14) proteins. Here we report the rationalization of the high potency of FR900359 and efforts towards understanding the G protein subtype selectivity by synthesis of a collection of structurally and stereochemically diverse analogs of YM-254890 using an efficient synthetic protocol. We performed the first conformational study of YM-254890 in aqueous solution by NMR spectroscopy and replica exchange molecular dynamics, which suggested that the combined contribution of residues with appropriate size, stereochemistry and conformational stability are critical for inhibitory potency. Moreover, in addition to the fit of the binding pocket, more factors should be taken into consideration for the development of compounds targeting other G proteins. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Discovery of ASP5286: A novel non-immunosuppressive cyclophilin inhibitor for the treatment of HCV
  作者：Takuya Makino、Seiji Yoshimura、Masahiro Neya、Toshio Yamanaka、Masae Sawada、Eisaku Tsujii、David Barrett

  DOI：10.1016/j.bmcl.2020.127308

  日期：2020.8

  Evidence indicates that hepatitis C virus (HCV) utilizes cellular cyclophilin proteins in its replication, and cyclophilin inhibitors represent a new class of anti-HCV agents. We have established an efficient synthetic methodology to generate FR901459 derivatives via N, O-acyl migration reaction while avoiding total synthesis. Through a detailed structure-activity relationship study, we improved anti-HCV activity while decreasing immunosuppressive activity. Additionally, we discovered the importance of substitution at the 3 position for not only improving anti-HCV activity but also pharmacokinetic profile. Finally, by striking an appropriate balance between potency, solubility, and permeability, we discovered ASP5286 (13) as a potential clinical candidate for anti-HCV therapy.