[(E,2S,3R,4R)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-benzylsulfanyl-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-2-oxoethyl]-methylamino]-1-oxobutan-2-yl]amino]-4-methyl-2-[methyl-[(2S)-3-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2S)-4-methyl-2-(methylamino)pentanoyl]amino]pentanoyl]amino]butanoyl]amino]-1-oxooct-6-en-3-yl] acetate | 159391-94-3

• 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: [(E,2S,3R,4R)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-benzylsulfanyl-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-2-oxoethyl]-methylamino]-1-oxobutan-2-yl]amino]-4-methyl-2-[methyl-[(2S)-3-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2S)-4-methyl-2-(methylamino)pentanoyl]amino]pentanoyl]amino]butanoyl]amino]-1-oxooct-6-en-3-yl] acetate
• CAS: 159391-94-3
• 化学式: C₆₈H₁₁₆N₁₀O₁₂S
• 分子量: 1297.79
• InChiKey: BRHUSIZJXPJPOF-ZCAGXOGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10
• 重原子数：
  91
• 可旋转键数：
  40
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  290
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  FMOC-L-谷氨酰胺 、 [(E,2S,3R,4R)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-benzylsulfanyl-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-2-oxoethyl]-methylamino]-1-oxobutan-2-yl]amino]-4-methyl-2-[methyl-[(2S)-3-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2S)-4-methyl-2-(methylamino)pentanoyl]amino]pentanoyl]amino]butanoyl]amino]-1-oxooct-6-en-3-yl] acetate 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of [d-lysine]8cyclosporin A analogs as potential anti-HCV agents

  摘要：

  An efficient synthesis of [D-lysine](8)cyclosporin A has been developed. Several analogs of [ D- lysine] 8cyclosporin A have been synthesized and show promising anti-HCV activity, particularly compounds 39 and 43, which each exhibit an anti-HCV EC50 < 200 nM, and are each >= 50-fold less immunosuppressive than cyclosporin A. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.036
• 作为产物：
  描述：

  O-Acetyl-N-(phenylthiocarbamoyl)-7,8-secocyclosporin-7-thiocarboxylic acid S-benzyl ester 在 盐酸 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以75%的产率得到[(E,2S,3R,4R)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-benzylsulfanyl-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-2-oxoethyl]-methylamino]-1-oxobutan-2-yl]amino]-4-methyl-2-[methyl-[(2S)-3-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2S)-4-methyl-2-(methylamino)pentanoyl]amino]pentanoyl]amino]butanoyl]amino]-1-oxooct-6-en-3-yl] acetate
  参考文献：
  名称：

  Cyclosporin A: Regioselective Ring Opening and Fragmentation Reactions via Thioamides. A Route to Semisynthetic Cyclosporins

  摘要：

  Cyclosporin A (1a) served as the starting material for the semisynthetic preparation of a variety of novel cyclosporins. Acetylcyclosporin A (2) was treated with Lawesson's reagent. From the reaction mixture, three novel acetylated thioamides were isolated: the 4,7-bis(thioamide) 3a, the 7-thioamide 3b, and the 4-thioamide 3c. The acetylated products 3a-c were hydrolyzed to the known thioamides 4a-c, respectively. The 7-thioamide 3b was alkylated to give the S-benzyl thioamidate 5b. A regioselective ring opening reaction at the activated site was induced by treating 5b under acidic conditions giving the 7,8-seco-cyclosporin 7a. The (R)-alanine moiety was replaced by (R)-phenylalanine via the Edman degradation product 7e giving 7f. Removal of the protecting groups led to 7h. This was cyclized to [(R)-phenylalanine](8)-cyclosporin (1b). The N-protected 7,8-seco-cyclosporin 7i was reduced to the aldehyde 7j, homologated (7k), and deprotected to give 7m. This was cyclized to the vinylogous cyclosporin 8a. Similarly,:the 4,5-seco-cyclosporin 9c was prepared and converted via several steps (9d-h) to the vinylogous cyclosporin 8b. Finally, under acidic conditions, the dibenzyl bis(thioamidate) 5a underwent a fragmentation reaction to give the octapeptide 10a and the tripeptide 11a. The octapeptide 10a was coupled with a different tripeptide (11d) to 9i and cyclized via 9j-k to the [(S)-phenylalanine](7)-cyclosporin (1c).

  DOI：

  10.1021/jo00103a015

文献信息

• Preparation and in Vitro Activities of Ethers of [D-Serine]8-cyclosporin
  作者：Marcel K. Eberle、Peter Hiestand、Anne-Marie Jutzi-Eme、Francois Nuninger、Hans R. Zihlmann

  DOI：10.1021/jm00011a004

  日期：1995.5

  ic acid]8-cyclosporin (39). The [2-ethoxy-5-morpholinecarboxylic acid]8-cyclosporin 40 was prepared via 36. Base treatment of the bromoacetate 37 gave the morpholinone derivative 41. [4(R)-Oxazolidinecarboxylic acid]8-cyclosporin (42) was obtained from 2 and methylene bromide. From 24 the tosylate 38 was prepared and cyclized to the hexahydrooxazepine derivative 43. [2(R)- Piperidinecarboxylic acid]8-cyclosporin

  [D-丝氨酸] 8-环孢菌素（2）与一系列烷基化剂在相转移条件下的反应得到烷基化产物3-6。2与溴乙酸受阻酯的烷基化反应得到结晶酯7和8。在碱性条件下水解，得到酸10。酯8还原生成新的环孢菌素11。在另外两个步骤中将其转化为15。在相似的两个步骤中从15制备步骤序列17。由2获得2-（溴甲基）丙烯酸甲酯产物20。2与49烷基化，然后脱保护，得到24。制备了线性异构体27。3-羟丙基醚30由28分两步制备。4-羟丁基醚31可从2和1，4-二溴丁烷中获得。11的羟基转化为甲苯磺酸酯32。32的碱处理导致产生双环[3（R）-吗啉羧酸] 8-环孢菌素（39）。经由[36]制备[2-乙氧基-5-吗啉羧酸] 8-环孢菌素40。对溴乙酸酯37进行碱处理，得到吗啉酮衍生物41。[4（R）-恶唑烷羧酸] 8-环孢菌素（42）从以下获得。 2和亚甲基溴。从24制备甲苯磺酸酯38，并将其环化为六氢氧杂ze庚因衍生物43。[42（R）-哌啶羧酸]
• Synthesis and Characterization of Bodipy-FL-Cyclosporine A as a Substrate for Multidrug Resistance-Linked P-Glycoprotein (ABCB1)
  作者：Andaleeb Sajid、Natarajan Raju、Sabrina Lusvarghi、Shahrooz Vahedi、Rolf E. Swenson、Suresh V. Ambudkar

  DOI：10.1124/dmd.119.087734

  日期：2019.10

  Fluorescent conjugates of drugs can be used to study cellular functions and pharmacology. These compounds interact with proteins as substrates or inhibitors, helping in the development of unique fluorescence-based methods to study in vivo localization and molecular mechanisms. P-glycoprotein (P-gp, ABCB1) is an ATP-binding cassette (ABC) transporter that effluxes most anticancer drugs from cells, contributing

  药物的荧光缀合物可用于研究细胞功能和药理学。这些化合物与作为底物或抑制剂的蛋白质相互作用，有助于开发独特的基于荧光的方法来研究体内定位和分子机制。P-糖蛋白（P-gp，ABCB1）是一种ATP结合盒（ABC）转运蛋白，可从细胞中排出大多数抗癌药物，从而促进了耐药性的发展。为了研究P-gp的转运功能，我们合成了Bodipy标记的环孢菌素A（BD-CsA）荧光偶联物。合成并表征其化学纯度后，将BD-CsA与常用的7-硝基苯-2-氧杂-1,3-二唑-4-基（NBD）-CsA探针进行了比较。在流式细胞仪检测中，BD-CsA的荧光强度几乎是NBD-CsA的荧光强度的10倍，使我们能够使用低得多的BD-CsA浓度来达到相同的荧光水平。我们发现BD-CsA被人类和小鼠P-gp识别为转运底物。人P-gp对BD-CsA的外排率与NBD-CsA相当。tariquidar抑制了BD-CsA的运输，其IC50值与