hirsutide | 865368-30-5

• 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: hirsutide
• 英文别名: cyclo(L-Phe-L-N-(Me)Phe-L-Val-L-N-(Me)Phe)；(3S,6S,9S,12S)-3,6,12-tribenzyl-1,7-dimethyl-9-propan-2-yl-1,4,7,10-tetrazacyclododecane-2,5,8,11-tetrone
• CAS: 865368-30-5
• 化学式: C₃₄H₄₀N₄O₄
• 分子量: 568.716
• InChiKey: YJRWOFGXVILYEW-KRCBVYEFSA-N

物化性质

• 沸点：
  844.0±65.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：可溶； DMSO：可溶；乙醇：可溶；甲醇：可溶

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  hirsutide 、 N-A-(2,4-二硝基-5-氟苯基)-L-丙氨酸 在 盐酸 、 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 反应 16.67h， 生成 L-Phe-L-FDAA 、 (S)-2-(5-((S)-1-amino-1-oxopropan-2-ylamino)-2,4-dinitrophenylamino)-3-methylbutanoic acid
  参考文献：
  名称：

  Insights into the Biosynthetic Origin of 3-(3-Furyl)alanine in Stachylidium sp. 293 K04 Tetrapeptides

  摘要：

  The marine-sponge-derived fungus Stachylidium sp. 293 K04 produces the N-methylated peptides endolide A (1) and endolide B (2), showing affinity for the vasopressin receptor 1A and serotonin receptor 5HT(2B), respectively. Both peptides feature the rare amino acid 3-(3-furyl)alanine. Isotope labeling experiments, employing several C-13-enriched precursors, revealed that this unprecedented heterocyclic amino acid moiety in endolide A (1) is synthesized from a cyclic intermediate of the shikimate pathway, but not from phenylalanine. Two new tetrapeptide analogues, endolides C and D (3 and 4), were characterized, as well as the previously described hirsutide (5).

  DOI：

  10.1021/acs.jnatprod.6b00601
• 作为产物：
  描述：

  L-Phe-L-N-(Me)Phe-L-Val-L-N-(Me)Phe-Opfp 在 N-甲基吗啉 、 吡啶 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 168.0h， 生成 hirsutide
  参考文献：
  名称：

  Toward the synthesis and biological evaluation of hirsutide

  摘要：

  The present investigation deals with the synthesis of a N-methylated cyclotetrapeptide, hirsutide (2), by coupling of the dipeptide units Boc-L-phenylalanyl-L-N-methylphenylalanine-OH and L-valyl-L-N-methylphenylalanine-OMe followed by cyclization of the linear tetrapeptide fragment. The chemical structure was established on the basis of analytical as well as spectroscopic data. The newly synthesized cyclic peptide was subjected to pharmacological screening and found to be highly potent against the gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae at 6 mu g cm(-3). In addition, potent antihelmintic activity against the earthworms Megascoplex konkanensis and Pontoscotex corethruses at 1 and 2 mg cm(-3), and potent cytotoxic activity against Dalton's lymphoma ascites and Ehrlich's ascites carcinoma cell lines with IC50 values of 14 and 22 mu M were also observed. Studies revealed that the pentafluorophenyl ester method employing a catalytic amount of N-methylmorpholine proved to be better for cyclization of the linear tetrapeptide unit.

  DOI：

  10.1007/s00706-008-0052-z

文献信息

• Insights into the Biosynthetic Origin of 3-(3-Furyl)alanine in <i>Stachylidium</i> sp. 293 K04 Tetrapeptides
  作者：Fayrouz El Maddah、Stefan Kehraus、Mamona Nazir、Celso Almeida、Gabriele M. König

  DOI：10.1021/acs.jnatprod.6b00601

  日期：2016.11.23

  The marine-sponge-derived fungus Stachylidium sp. 293 K04 produces the N-methylated peptides endolide A (1) and endolide B (2), showing affinity for the vasopressin receptor 1A and serotonin receptor 5HT(2B), respectively. Both peptides feature the rare amino acid 3-(3-furyl)alanine. Isotope labeling experiments, employing several C-13-enriched precursors, revealed that this unprecedented heterocyclic amino acid moiety in endolide A (1) is synthesized from a cyclic intermediate of the shikimate pathway, but not from phenylalanine. Two new tetrapeptide analogues, endolides C and D (3 and 4), were characterized, as well as the previously described hirsutide (5).
• Toward the synthesis and biological evaluation of hirsutide
  作者：Rajiv Dahiya、Monika Maheshwari、Anil Kumar

  DOI：10.1007/s00706-008-0052-z

  日期：2009.1

  The present investigation deals with the synthesis of a N-methylated cyclotetrapeptide, hirsutide (2), by coupling of the dipeptide units Boc-L-phenylalanyl-L-N-methylphenylalanine-OH and L-valyl-L-N-methylphenylalanine-OMe followed by cyclization of the linear tetrapeptide fragment. The chemical structure was established on the basis of analytical as well as spectroscopic data. The newly synthesized cyclic peptide was subjected to pharmacological screening and found to be highly potent against the gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae at 6 mu g cm(-3). In addition, potent antihelmintic activity against the earthworms Megascoplex konkanensis and Pontoscotex corethruses at 1 and 2 mg cm(-3), and potent cytotoxic activity against Dalton's lymphoma ascites and Ehrlich's ascites carcinoma cell lines with IC50 values of 14 and 22 mu M were also observed. Studies revealed that the pentafluorophenyl ester method employing a catalytic amount of N-methylmorpholine proved to be better for cyclization of the linear tetrapeptide unit.