N-BOC-Val-MeLeu-Phe-OH | 159392-23-1

• 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: N-BOC-Val-MeLeu-Phe-OH
• 英文别名: Boc-Val-N(Me)Leu-Phe-OH；(2S)-2-[[(2S)-4-methyl-2-[methyl-[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]pentanoyl]amino]-3-phenylpropanoic acid
• CAS: 159392-23-1
• 化学式: C₂₆H₄₁N₃O₆
• 分子量: 491.628
• InChiKey: DIJIADOUUPNDNR-ACRUOGEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-BOC-Val-MeLeu-Phe-OH 、 [(E,2S,3R,4R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-aminopropanoyl]-methylamino]-4-methylpentanoyl]-methylamino]-4-methylpentanoyl]-methylamino]-3-methylbutanoyl]-methylamino]-1-[[(2S)-1-[[2-[[(2S)-1-benzylsulfanyl-4-methyl-1-oxopentan-2-yl]-methylamino]-2-oxoethyl]-methylamino]-1-oxobutan-2-yl]amino]-4-methyl-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 2.0h， 以47%的产率得到O-Acetyl-N-BOC-4,5-seco-<(S)-phenylalanine>⁷-cyclosporin-4-thiocarboxylic acid S-benzyl ester
  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：

  L-苯丙氨酸苄酯对甲苯磺酸盐 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 N-BOC-Val-MeLeu-Phe-OH
  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).