asperphenamate | 63631-36-7

• 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: asperphenamate
• 英文别名: anabellamide；auranamide；[(2S)-2-benzamido-3-phenylpropyl] (2S)-2-benzamido-3-phenylpropanoate
• CAS: 63631-36-7
• 化学式: C₃₂H₃₀N₂O₄
• 分子量: 506.601
• InChiKey: CVULDJMCSSACEO-VMPREFPWSA-N

物化性质

• 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)：
  6.1
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

生物活性

Asperphenamate 是来自 Aspergillus flavipes 的真菌代谢物，具有抗肿瘤活性。其对 T47D、MDA-MB-231 和 HL-60 细胞的 IC50 值分别为 92.3 μM、96.5 μM 和 97.9 μM。

体外研究

Asperphenamate 能通过完全诱导自噬来抑制癌细胞增殖。此外，它对溶酶体蛋白水解酶 cathepsin L 具有抑制作用，同时对 cathepsin S 的抑制能力较弱。

反应信息

• 作为反应物：
  描述：

  asperphenamate 在 sodium hydroxide 作用下， 生成 (S)-N-(1-hydroxy-3-phenylpropan-2-yl)benzamide
  参考文献：
  名称：

  Banerji, Avijit; Ray, Rita, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1981, vol. 20, # 7, p. 597 - 598

  摘要：

  DOI：
• 作为产物：
  描述：

  (S)-(S)-2-benzamido-3-phenylpropyl 2-(tert-butoxycarbonylamino)-3-phenylpropanoate 在 吡啶 、 盐酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 生成 asperphenamate
  参考文献：
  名称：

  Synthesis and in vitro antitumor activity of asperphenamate derivatives as autophagy inducer

  摘要：

  In an effort to improve the aqueous solubility and the antitumor activity of natural product asperphenamate, we have designed and synthesized three series of asperphenamate derivatives, including series I (simplifying molecular skeleton series), series II (introducing a hydroxyl group to A-phenyl ring series) and series III (disrupting molecular planarity series). All derivatives have displayed a significantly increased solubility compared with asperphenamate. Their growth inhibitory activities in vitro were screened by the standard MTT method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the derivatives in series I, most of derivatives in series II and series III showed growth inhibitory activity. Among all derivatives, IM23b in series III showed the greatest potency in human breast cancer MCF-7 cells. The cellular potency of IM23b was approximately 1.5-fold more potent than that of cisplatin. The mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was further investigated. We concluded that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.101

文献信息

• Asperphenamate biosynthesis reveals a novel two-module NRPS system to synthesize amino acid esters in fungi
  作者：Wei Li、Aili Fan、Long Wang、Peng Zhang、Zhiguo Liu、Zhiqiang An、Wen-Bing Yin

  DOI：10.1039/c7sc02396k

  日期：——

  a group of structurally diverse natural products with distinct activities. Some are synthesized through an inter-molecular esterification step catalysed by nonribosomal peptide synthetase (NRPS). In bacteria, the formation of the intra-molecular ester bond is usually catalysed by a thioesterase domain of NRPS. However, the mechanism by which fungal NRPSs perform this process remains unclear. Herein

  氨基酸酯是一组结构多样、具有独特活性的天然产物。有些是通过非核糖体肽合成酶 (NRPS) 催化的分子间酯化步骤合成的。在细菌中，分子内酯键的形成通常由 NRPS 的硫酯酶结构域催化。然而，真菌 NRPS 执行这一过程的机制仍不清楚。在此，通过短致青霉中的靶向基因破坏和构巢曲霉中的异源表达，我们表明两种NRPS，ApmA和ApmB，足以合成氨基酸酯asperphenamate。使用异源表达系统，我们发现具有还原酶结构域的 ApmA 很少产生二肽醇。相比之下，ApmB 不仅能催化分子间酯键的形成，还能将线性二肽基前体接受到 NRPS 链中。这里描述的机制提供了一种以 NRPS 作为催化剂合成新小分子的方法。我们的研究首次揭示了自然界中氨基酸酯形成的双模块 NRPS 系统。
• Total synthesis and anticancer activity studies of the stereoisomers of asperphenamate and patriscabratine
  作者：Lei Yuan、Jin Hui Wang、Tie Min Sun

  DOI：10.1016/j.cclet.2009.10.004

  日期：2010.2

  All stereoisomers of asperphenamate 1a and patriscabratine 2a were achieved with a high yield, and total synthesis of 2a is firstly described here. The absolute configuration of patriscabratine was determined as (S,S). The compounds 1a-d and 2a-d have been tested by MTT assay in T47D, MDA-MB231, HL60, Hela and SGC-7901 cell lines in vitro. Among them, the (R,S) stereoisomer shows the strongest anticancer effects, while the (S,R) shows the weakest one. (C) 2009 Tie Min Sun. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
• Synthesis and in vitro antitumor activity of asperphenamate derivatives as autophagy inducer
  作者：Lei Yuan、Yanchun Li、Chunyang Zou、Chao Wang、Jian Gao、Caixia Miao、Enlong Ma、Tiemin Sun

  DOI：10.1016/j.bmcl.2012.01.101

  日期：2012.3

  In an effort to improve the aqueous solubility and the antitumor activity of natural product asperphenamate, we have designed and synthesized three series of asperphenamate derivatives, including series I (simplifying molecular skeleton series), series II (introducing a hydroxyl group to A-phenyl ring series) and series III (disrupting molecular planarity series). All derivatives have displayed a significantly increased solubility compared with asperphenamate. Their growth inhibitory activities in vitro were screened by the standard MTT method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the derivatives in series I, most of derivatives in series II and series III showed growth inhibitory activity. Among all derivatives, IM23b in series III showed the greatest potency in human breast cancer MCF-7 cells. The cellular potency of IM23b was approximately 1.5-fold more potent than that of cisplatin. The mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was further investigated. We concluded that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. (C) 2012 Elsevier Ltd. All rights reserved.
• Banerji, Avijit; Ray, Rita, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1981, vol. 20, # 7, p. 597 - 598
  作者：Banerji, Avijit、Ray, Rita

  DOI：——

  日期：——