Cyclosporin 4-(benzyl thioamidate) | 159391-90-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: Cyclosporin 4-(benzyl thioamidate)
• 英文别名: (6S,9S,12S,15S,18S,21R,24S,27S,30S,33S)-32-benzylsulfanyl-6-ethyl-9-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,10,13,16,19,21,24,28-nonamethyl-15,18,27,33-tetrakis(2-methylpropyl)-12,30-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-31-ene-2,5,8,11,14,17,20,23,26,29-decone
• CAS: 159391-90-9
• 化学式: C₆₉H₁₁₇N₁₁O₁₁S
• 分子量: 1308.82
• InChiKey: GCCCWBOVKFJXCT-RQEOLKSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  92
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  287
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  Cyclosporin 4-(benzyl thioamidate) 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 3.0h， 生成 4,5-Secocyclosporin
  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
• 作为产物：
  描述：

  O-acetyl-cyclosporin A 在 劳森试剂 、 sodium hydroxide 、 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 、 xylene 为溶剂， 反应 3.5h， 生成 Cyclosporin 4-(benzyl thioamidate)
  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

• Cyclosporin A: Regioselective Ring Opening and Fragmentation Reactions via Thioamides. A Route to Semisynthetic Cyclosporins
  作者：Marcel K. Eberle、Anne-Marie Jutzi-Eme、Francois Nuninger

  DOI：10.1021/jo00103a015

  日期：1994.12

  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).