tert-butyl (S)-(1-oxo-3-(tritylthio)propan-2-yl)carbamate | 175357-57-0

• 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: tert-butyl (S)-(1-oxo-3-(tritylthio)propan-2-yl)carbamate
• 英文别名: N-(tert-butoxy-carbonyl)-S-triphenylmethylcysteine aldehyde；tert-butyl N-[(2S)-1-oxo-3-tritylsulfanylpropan-2-yl]carbamate
• CAS: 175357-57-0
• 化学式: C₂₇H₂₉NO₃S
• 分子量: 447.598
• InChiKey: BVIZOEBRLRZHGI-DEOSSOPVSA-N

物化性质

• 沸点：
  566.8±50.0 °C(Predicted)
• 密度：
  1.151±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  32.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  55.4
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(1-oxo-3-(tritylthio)propan-2-yl)carbamate 在 2,6-二甲基吡啶 、 三氟甲磺酸三甲基硅酯 、 potassium carbonate 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 5.0h， 生成 (E)-(S)-4-Amino-2-methyl-5-tritylsulfanyl-pent-2-enoic acid allyl ester
  参考文献：
  名称：

  系统化学诱变鉴定了一种有效的新型 Apratoxin A/E 杂交体，具有改善的体内抗肿瘤活性

  摘要：

  Apratoxins 是具有细胞毒性的海洋天然产物，可防止分泌途径早期的共翻译易位。我们发现 apratoxin 会下调受体和生长因子配体，对癌细胞，特别是那些依赖自分泌环的细胞，给予一到两次的打击。通过全合成，我们测试了氨基酸取代（包括丙氨酸扫描）对受体酪氨酸激酶和血管内皮生长因子 A（VEGF-A）下调的影响，并通过选定手性中心的差向异构化探测了靶标参与的立体特异性。对两种分泌分子的不同作用表明，可以通过结构修饰调整阿普雷毒素对分泌抑制的底物选择性，以提供量身定制的治疗。

  DOI：

  10.1021/ml200176m
• 作为产物：
  描述：

  (S)-N-methyl-N-methoxy-2-tert-butoxycarbonylamino-3-(triphenylmethylthio)propionamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 生成 tert-butyl (S)-(1-oxo-3-(tritylthio)propan-2-yl)carbamate
  参考文献：
  名称：

  Ulbactin F（一种铁结合天然产物）的生物启发全合成

  摘要：

  来自环境微生物组的天然产物为阐明新药寻找中的生物活性提供了精美的模板。最近发现的一种海洋短芽孢杆菌。代谢物 ulbactin F 被发现可抑制肿瘤细胞迁移和侵袭，IC 50 < 3 μM。在此，我们公开了 ulbactin F 和epi -ulbactin F的首次全合成，这是根据生物合成途径建模的。该支架与人类病原体的铁载体结构相似，但包含源自半胱氨酸的新型三环系统。我们发现ulbactin F形成低亲和力金属配合物，优先选择Fe 3+和Cu 2+，这可能暗示了其环境作用及其抗转移作用机制。

  DOI：

  10.1021/acs.orglett.8b02599

文献信息

• Synthesis of threo-β-aminoalcohols from aminoaldehydes via chelation-controlled additions. Total synthesis of l-threo sphingosine and safingol
  作者：Michael E. Jung、Sung Wook Yi

  DOI：10.1016/j.tetlet.2012.05.153

  日期：2012.8

  threo-β-amino alcohol derivatives through chelation with the carbamoyl moiety. The carbamate group is a stronger chelating group than other potentially good chelators, for example ethers, esters, thioethers, and gives good diastereoselectivity with cuprates. Thus addition of lithium divinylcuprate to the aldehyde generated from the serine derivative 25 in the presence of extra copper for chelation

  由功能化氨基酸制备的N-氨基甲酰基氨基醛螯合控制的有机铜酸酯的添加主要通过与氨基甲酰基部分的螯合生成苏-β-氨基醇衍生物。氨基甲酸酯基团是比其他潜在的良好螯合剂（例如醚，酯，硫醚）更强的螯合基团，并且对铜酸盐具有良好的非对映选择性。因此，在额外的铜的存在下，将二乙烯基铜酸锂添加到由丝氨酸衍生物25产生的醛中进行螯合，以83％的收率得到苏式化合物26。保护基团的交叉复分解和裂解提供了l-苏式鞘氨醇21。另外，通过这种方法，由市售的O-苄基N -BOC丝氨酸28以六个步骤制备了溶血鞘脂蛋白激酶C抑制剂safingol，22，其总产率为56％。
• Method of treating cancer
  申请人：Rosen Neal

  公开号：US20050137207A1

  公开（公告）日：2005-06-23

  The present invention relates to methods of treating cancer using a combination of a compound which is an antineoplastic agent and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is an antineoplastic agent and a compound which is a inhibitor of prenyl-protein transferase. The invention also relates to methods of preparing such compositions.

  本发明涉及使用一种抗肿瘤剂和一种前尼蛋白转移酶抑制剂的组合治疗癌症的方法，该方法包括向所述哺乳动物施用来自以下组中至少两种治疗剂的量，所述组包括一种抗肿瘤剂和一种前尼蛋白转移酶抑制剂，所述治疗剂可以按任何顺序依次或同时施用。该发明还涉及制备这种组合物的方法。
• [EN] MACROCYCLIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE, AND METHODS OF TREATMENT<br/>[FR] AGENTS THÉRAPEUTIQUES MACROCYCLIQUES, DES MÉTHODES DE FABRICATION, ET MÉTHODES DE TRAITEMENT
  申请人：UNIV FLORIDA

  公开号：WO2015127161A1

  公开（公告）日：2015-08-27

  The instant invention describes macrocyclic compounds having therapeutic activity, and the mechanism and methods of treating disorders such as autoimmune diseases, inflammation, and cancer, tumors and cell proliferation related disorders.

  本发明描述了具有治疗活性的大环化合物，以及治疗自身免疫疾病、炎症、癌症、肿瘤和与细胞增殖有关的疾病的机制和方法。
• JAK KINASE INHIBITOR AND PREPARATION AND APPLICATION THEREOF
  申请人：Minghui Pharmaceutical (Shanghai) Limited

  公开号：EP4119565A1

  公开（公告）日：2023-01-18

  The present invention provides a JAK kinase inhibitor and a preparation and application thereof, and the present invention specifically provides a compound having a structure represented in the following formula I, an enantiomer thereof, or a pharmaceutically acceptable salt thereof. The compound has uniquely advantageous JAK kinase inhibitory activity, and as such may be used for treatment of a disease or illness related to JAK kinase activity or expression level.

  本发明提供一种JAK激酶抑制剂及其制备方法和应用，并且具体地提供一种具有以下结构式I的化合物、其对映体，或者其药学上可接受的盐。该化合物具有独特优势的JAK激酶抑制活性，因此可用于治疗与JAK激酶活性或表达水平相关的疾病或病症。
• 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.