fellutamide B

• 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: fellutamide B
• 英文别名: (2S)-2-[[(2S)-4-amino-2-[[(3R)-3-hydroxydodecanoyl]amino]-4-oxobutanoyl]amino]-N-[(2S)-4-methyl-1-oxopentan-2-yl]pentanediamide
• 化学式: C₂₇H₄₉N₅O₇
• 分子量: 555.715
• InChiKey: MFXAGCQVWGPEJH-LRSLUSHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  39
• 可旋转键数：
  23
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  211
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  fellutamide B 在 potassium permanganate 作用下， 以 水 为溶剂， 反应 0.5h， 生成 (2S)-2-[[(2S)-5-amino-2-[[(2S)-4-amino-2-[[(3R)-3-hydroxydodecanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoic acid
  参考文献：
  名称：

  Seven New and Two Known Lipopeptides as well as Five Known Polyketides: The Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy Using Diethyl Sulphate

  摘要：

  AD-2-1 是一种抗肿瘤真菌突变体，它是通过硫酸二乙酯诱变海洋源青霉菌 G59 获得的。在使用 K562 细胞进行的 MTT 试验中，G59 菌株原本不产生任何具有抗肿瘤活性的代谢物。在 MTT 试验和 TLC 分析的指导下，通过与对照 G59 提取物的直接比较，对新产生的代谢物进行了追踪，从突变体 AD-2-1 的提取物中分离出了七种新的（1-7）和两种已知的（8-9）脂肽，以及五种已知的多酮类化合物 10-14。通过光谱和化学证据确定了七种新化合物的结构及其绝对构型，并将其命名为青霉酰胺 A-G（1-7）。七个已知化合物被鉴定为fellutamide B (8)、fellutamide C (9)、1′-O-methylaverantin (10)、averantin (11)、averufin (12)、nidurufin (13) 和 sterigmatocystin (14)。在 MTT 试验中，1-14 对几种人类癌细胞株有不同程度的抑制作用。所有生物测定和高效液相色谱-光电二极管阵列检测器（PDAD）-紫外和高效液相色谱-电子喷雾电离（ESI）-质谱分析表明，突变体 AD-2-1 中 1-14 的产生是由原始 G59 真菌菌株中沉默代谢物的活化产生引起的。本研究结果为利用硫酸二乙酯诱变的化学诱变策略通过激活真菌分离物中的沉默代谢物来发现新化合物的有效性提供了更多实例。

  DOI：

  10.3390/md12041815
• 作为产物：
  描述：

  L-谷氨酰胺 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 fellutamide B
  参考文献：
  名称：

  Solution phase synthetic approach to fellutamide B

  摘要：

  A convenient solution phase approach for the synthesis of fellutamide B with efficient purification techniques has been demonstrated on the molecule for the first time. The strategy involves the use of natural amino acids as starting materials and classical peptide coupling reactions. The synthesis has been achieved in 10 steps with overall yield of 26.7% making the synthesis facile. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2015.04.037

文献信息

• Total Synthesis of Fellutamide B and Deoxy-Fellutamides B, C, and D
  作者：Andrew Giltrap、Katie Cergol、Angel Pang、Warwick Britton、Richard Payne

  DOI：10.3390/md11072382

  日期：——

  The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative

  报告了海洋衍生的脂肽天然产物 flutamide B 和脱氧 fellutamides B、C 和 D 的全合成。这些化合物是通过使用 Weinreb 酰胺衍生树脂的新型固相合成策略获得的。作为合成的一部分，利用布朗烯丙基化反应和氧化裂解-氧化序列作为关键步骤开发了一种新的 (3R)-羟基月桂酸的对映选择性路线。这些天然产物和天然产物类似物的活性也在体外针对结核分枝杆菌进行了评估。
• Neurotrophic peptide aldehydes: Solid phase synthesis of fellutamide B and a simplified analog
  作者：John S. Schneekloth、John L. Sanders、John Hines、Craig M. Crews

  DOI：10.1016/j.bmcl.2006.04.029

  日期：2006.7

  have been used to complete the total synthesis of the neurotrophic lipopeptide aldehyde fellutamide B (2). The beta-hydroxy aliphatic tail was prepared by regioselective reductive opening of a cyclic sulfate, and later coupled to a solid phase resin. The synthetic compound was then examined in cytotoxicity and nerve growth factor (NGF) induction assays. A simplified analog of fellutamide B also showed

  已使用固相和液相合成方法的组合来完成神经营养性脂肽醛非鲁胺 B (2) 的全合成。β-羟基脂肪族尾部是通过环状硫酸盐的区域选择性还原开环制备的，然后与固相树脂偶联。然后在细胞毒性和神经生长因子 (NGF) 诱导试验中检查合成化合物。非鲁胺 B 的简化类似物也显示出活性。
• Total synthesis of fellutamides, lipopeptide proteasome inhibitors. More sustainable peptide bond formation
  作者：Michael C. Pirrung、Fa Zhang、Sudhakar Ambadi、Y. Gangadhara Rao

  DOI：10.1039/c6ob01233g

  日期：——

  Solution-phase syntheses of three bioactive natural products of mixed polypeptide–polyketide biogenesis, fellutamides A, B, and C, have been achieved. Three peptide bonds are generated without the use of coupling reagents in each synthesis of the fellutamides, which act against proteasomes.

  已实现了三种生物活性天然产物的混合多肽-聚酮化合物生物合成，氟尿酰胺A，B和C的溶液相合成。在氟尿酰胺的每个合成过程中，在不使用偶联剂的情况下生成了三个肽键，它们可抵抗蛋白酶体。
• Solution phase synthetic approach to fellutamide B
  作者：Jhillu Singh Yadav、Soma Shekar Dachavaram、René Grée、Saibal Das

  DOI：10.1016/j.tetlet.2015.04.037

  日期：2015.6

  A convenient solution phase approach for the synthesis of fellutamide B with efficient purification techniques has been demonstrated on the molecule for the first time. The strategy involves the use of natural amino acids as starting materials and classical peptide coupling reactions. The synthesis has been achieved in 10 steps with overall yield of 26.7% making the synthesis facile. (C) 2015 Elsevier Ltd. All rights reserved.
• Seven New and Two Known Lipopeptides as well as Five Known Polyketides: The Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy Using Diethyl Sulphate
  作者：Chang-Jing Wu、Chang-Wei Li、Cheng-Bin Cui

  DOI：10.3390/md12041815

  日期：——

  AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derived Penicillium purpurogenum G59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (1–7) and two known (8–9) lipopeptides were isolated together with five known polyketides 10–14 from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A–G (1–7). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1′-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay, 1–14 inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of 1–14 in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.

  AD-2-1 是一种抗肿瘤真菌突变体，它是通过硫酸二乙酯诱变海洋源青霉菌 G59 获得的。在使用 K562 细胞进行的 MTT 试验中，G59 菌株原本不产生任何具有抗肿瘤活性的代谢物。在 MTT 试验和 TLC 分析的指导下，通过与对照 G59 提取物的直接比较，对新产生的代谢物进行了追踪，从突变体 AD-2-1 的提取物中分离出了七种新的（1-7）和两种已知的（8-9）脂肽，以及五种已知的多酮类化合物 10-14。通过光谱和化学证据确定了七种新化合物的结构及其绝对构型，并将其命名为青霉酰胺 A-G（1-7）。七个已知化合物被鉴定为fellutamide B (8)、fellutamide C (9)、1′-O-methylaverantin (10)、averantin (11)、averufin (12)、nidurufin (13) 和 sterigmatocystin (14)。在 MTT 试验中，1-14 对几种人类癌细胞株有不同程度的抑制作用。所有生物测定和高效液相色谱-光电二极管阵列检测器（PDAD）-紫外和高效液相色谱-电子喷雾电离（ESI）-质谱分析表明，突变体 AD-2-1 中 1-14 的产生是由原始 G59 真菌菌株中沉默代谢物的活化产生引起的。本研究结果为利用硫酸二乙酯诱变的化学诱变策略通过激活真菌分离物中的沉默代谢物来发现新化合物的有效性提供了更多实例。