(R)-N-methyl-N-methoxy-2-tert-butoxycarbonylamino-3-(triphenylmethylthio)propionamide | 158861-38-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (R)-N-methyl-N-methoxy-2-tert-butoxycarbonylamino-3-(triphenylmethylthio)propionamide
• 英文别名: N-tert-butyloxycarbonyl-S-tritylcysteine weinrebamide；tert-butyl N-[(2R)-1-[methoxy(methyl)amino]-1-oxo-3-tritylsulfanylpropan-2-yl]carbamate
• CAS: 158861-38-2
• 化学式: C₂₉H₃₄N₂O₄S
• 分子量: 506.666
• InChiKey: PPCGNIONQKAWQY-VWLOTQADSA-N

物化性质

• 熔点：
  45-47 °C
• 密度：
  1.163±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  93.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N-methyl-N-methoxy-2-tert-butoxycarbonylamino-3-(triphenylmethylthio)propionamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以87 %的产率得到N-α-(tert-butoxycarbonyl)-S-(triphenylmethyl)-L-cysteinal
  参考文献：
  名称：

  通过化学合成和密度泛函理论计算推导的铁载体 Piscibactin 合成类似物中 Ga3+ 配位的结构要求

  摘要：

  进行了几种 piscibactin (Pcb) 类似物的立体选择性全合成，该类似物是由不同致病性革兰氏阴性菌产生的铁载体。酸敏感的 α -甲基噻唑啉部分被更稳定的噻唑环取代，不同之处在于 C-13 位置的 OH 基团的构型。这些 Pcb 类似物作为 Fe 3+的模拟物与 Ga 3+形成络合物的能力表明，C-13 处的羟基作为 13 S的构型对于 Ga 3+的螯合以保持金属配位至关重要，而噻唑环而不是α-甲基噻唑啉部分的存在不影响这种配位。一个完整的1C9/C10 附近的非对映异构体混合物的1H 和13 C NMR 化学位移分配用于诊断立体化学处置。此外，密度泛函理论计算不仅用于确认六种可能的非对映异构体中Ga 3+络合物的立体化学，还用于推断它们与镓形成八面体配位球的能力。最后，Pcb 和 Pcb 噻唑类似物 Ga 3+配合物对鳗弧菌缺乏抗菌活性同意铁载体在保护病原体免受金属离子毒性中的作

  DOI：

  10.1021/acs.inorgchem.3c00787
• 作为产物：
  描述：

  N-叔丁氧羰基-S-三苯甲基-L-半胱氨酸 在 N-甲基哌啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 生成 (R)-N-methyl-N-methoxy-2-tert-butoxycarbonylamino-3-(triphenylmethylthio)propionamide
  参考文献：
  名称：

  Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase

  摘要：

  Inhibitors of Ras farnesyl-protein transferase are described. These are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Deletion of the carbonyl groups between the first two residues of the tetrapeptides either preserves or improves activity, depending on the peptide sequence. The most potent in vitro enzyme inhibitor described (IC50 = 5 nM) is Cys[PSICH2NH]Ile[PSICH2NH]Phe-Met(3). To obtain compounds able to suppress Ras farnesylation in cell culture, further structural modification to include a homoserine lactone prodrug was required. Compound 18(Cys[PSICH2NH]Ile[PSICH2NH]Ile-homoserine lactone)reduced the extent of Ras farnesylation by 50 % in NIH3T3 fibroblasts in culture at a concentration of 50 muM. Structure-activity studies also led to 12 (Cys[PSICH2NH]Val-Ile-Leu), a potent and selective inhibitor of a related enzyme, the type-I geranylgeranyl protein transferase.

  DOI：

  10.1021/jm00032a004

文献信息

• Design and Synthesis of Non-Peptide Ras CAAX Mimetics as Potent Farnesyltransferase Inhibitors
  作者：Yimin Qian、Andreas Vogt、Saïd M. Sebti、Andrew D. Hamilton

  DOI：10.1021/jm950414g

  日期：1996.1.1

  These non-peptide mimetics are potent inhibitors of FTase (IC50 = 40 nM for the most potent inhibitor) and are highly selective for FTase over GGTase I (geranylgeranyltransferase I). They are not substrates for farnesylation, do not have peptidic features, and have no hydrolyzable bonds. Structure-activity studies reveal the importance of the position of the carboxylic acid on the aryl ring as well as

  ras癌基因产物Ras的半胱氨酸法呢基化对于其转化活性是必需的，并且被法呢基转移酶（FTase）催化。Ras羧基末端四肽CAAX（C是半胱氨酸，A是任何脂肪族氨基酸，X是蛋氨酸或丝氨酸）是FTase识别的最小序列。我们在这里报告Ras CAAX非肽模拟物的设计，合成和生物学特性，其中半胱氨酸通过还原的伪肽键与4-氨基-3'-羧基联苯相连。这些非肽模拟物是FTase的有效抑制剂（IC50 = 40 nM，是最有效的抑制剂），对FTase的选择性高于GGTase I（香叶基香叶基转移酶I）。它们不是法呢基化的底物，没有肽特征，也没有可水解键。结构活性研究揭示了芳基环上羧酸位置以及半胱氨酸酰胺键还原的重要性。在4-氨基-3'-羧基联苯的2-位取代可提高抑制能力，而羧酸的去除则会导致抑制活性降低10倍。
• Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity
  作者：Qi-Yin Chen、Yanxia Liu、Weijing Cai、Hendrik Luesch

  DOI：10.1021/jm4019965

  日期：2014.4.10

  Apratoxins are cytotoxic natural products originally isolated from marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pathway to downregulate receptor levels and inhibit growth factor secretion, leading to potent antiproliferative activity. Through rational design and total synthesis of an apratoxin A/ E hybrid, apratoxin S4 (1a), we have previously improved the antitumor activity and tolerability in vivo. Compound la and newly designed analogues apratoxins S7-S9 (1b-d), with various degrees of methylation at C34 (1b,c) or epimeric configuration at C30 (1d), were efficiently synthesized utilizing improved procedures. Optimizations have been applied to the synthesis of key intermediate aldehyde 7 and further include the application of Leighton's silanes and modifications of Kelly's methods to induce thiazoline ring formation in other crucial steps of the apratoxin synthesis. Apratoxin S9 (1d) exhibited increased activity with subnanomolar potency. Apratoxin S8 (lc) lacks the propensity to be deactivated by dehydration and showed efficacy in a human HCT116 xenograft mouse model.
• Convergent Synthesis of Peptide Nucleic Acids by Native Chemical Ligation
  作者：Christian Dose、Oliver Seitz

  DOI：10.1021/ol051489+

  日期：2005.9.1

  graph A convergent strategy for synthesizing long contiguous PNA by a native chemical ligation-like technique of PNA segment couplings is presented. This approach required the synthesis of a new PNA-monomer featuring a 1-amino-2-thiol group. It is shown that the additional mercaptomethyl group leaves the hybridization properties of PNA ligation products unaffected. Furthermore, rapid and efficient fluorescence labeling of the ligation products is demonstrated.
• Synthesis and Biological Activity of Kalkitoxin and its Analogues
  作者：Taiki Umezawa、Manabu Sueda、Takao Kamura、Teppei Kawahara、Xuerong Han、Tatsufumi Okino、Fuyuhiko Matsuda

  DOI：10.1021/jo201951s

  日期：2012.1.6

  Total syntheses of kalkitoxin, isolated from the Caribbean Lyngbya majuscula, and its analogues, 3-epi-, 7-epi-, 8-epi-, 10-epi-, 10-nor-, and 16-nor-kalldtcocin, were achieved via oxazolidinone-based diastereoselective 1,4-addition reaction of a methyl group and efficient T1C14-mediated thiazoline ring formation as the key steps. The biological activities of synthetic kalkitoxin and its analogues were evaluated with brine shrimp.
• MACROCYCLIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE, AND METHODS OF TREATMENT
  申请人：University of Florida Research Foundation

  公开号：EP3107919B1

  公开（公告）日：2021-01-27