(2S,3S,4S)-3-hydroxy-6-methoxy-3-methyl-7-methylidene-5-oxo-2-pentyl-2,3,4,5,6,7-hexahydropyrano[2,3-c]pyrrol-4-ylchloroacetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: (2S,3S,4S)-3-hydroxy-6-methoxy-3-methyl-7-methylidene-5-oxo-2-pentyl-2,3,4,5,6,7-hexahydropyrano[2,3-c]pyrrol-4-ylchloroacetate
• 英文别名: [(2S,3S,4S)-3-hydroxy-6-methoxy-3-methyl-7-methylidene-5-oxo-2-pentyl-2,4-dihydropyrano[2,3-c]pyrrol-4-yl] 2-chloroacetate
• 化学式: C₁₇H₂₄ClNO₆
• 分子量: 373.834
• InChiKey: JMQPFVBGPGRSGX-KCTSRDHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3S,4S)-3-hydroxy-6-methoxy-3-methyl-7-methylidene-5-oxo-2-pentyl-2,3,4,5,6,7-hexahydropyrano[2,3-c]pyrrol-4-ylchloroacetate 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 48.0h， 生成 (2S,3R,4R)-3-hydroxy-6-methoxy-3-methyl-7-methylidene-4-(morpholin-4-yl)-2-pentyl-3,4,6,7-tetrahydropyrano[2,3-c]pyrrol-5(2H)-one
  参考文献：
  名称：

  Synthesis of natural phaeosphaeride A and semi-natural phaeosphaeride B derivatives

  摘要：

  6-O-Acylated phaeosphaeride A and phaeosphaeride B in reaction with secondary cyclic amines undergo stereospecific replacement of acyloxy group by pharmacophoric amino moiety. In case of chloroacetoxy derivative, chlorine displacement by such amines proceeds in the presence of triethylamine.

  DOI：

  10.1016/j.mencom.2017.09.020
• 作为产物：
  描述：

  phaeosphaeride A 、 氯乙酰氯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以43%的产率得到(2S,3S,4S)-3-hydroxy-6-methoxy-3-methyl-7-methylidene-5-oxo-2-pentyl-2,3,4,5,6,7-hexahydropyrano[2,3-c]pyrrol-4-ylchloroacetate
  参考文献：
  名称：

  天然邻苯二酚A衍生物的合成及其抗癌潜力的体外评价

  摘要：

  合成了Phphasphaeride A（PPA）的衍生物并进行了表征；然后在A549癌细胞系上进行了抗癌研究。发现乙酰基衍生物（化合物3）具有与PPA相当的体外细胞毒性（分别为EC 50  = 49±7μM和EC 50  = 46±5μM），而氯乙酰基衍生物6（EC 50  = 33±发现7μM）对A549癌细胞系具有更好的功效。

  DOI：

  10.1016/j.bmcl.2015.10.048

文献信息

• Towards lead compounds as anti-cancer agents via new phaeosphaeride A derivatives
  作者：Victoria V. Abzianidze、Sofya A. Zakharenkova、Natalia I. Moiseeva、Petr P. Beltyukov、Valeriy A. Polukeev、Yaroslav A. Dubrovskii、Victor A. Kuznetsov、Yuri G. Trishin、Jennifer E. Mejia、Alvin A. Holder

  DOI：10.1016/j.bmcl.2018.11.003

  日期：2019.1

  New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor studies were carried out on the U937, HCT-116, PC3, MCF-7, A549, К562, NCI-H929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 (IC50 = 0.59 ± 0.27 µM) was observed to

  合成并表征了新的邻苯二酚A衍生物（PPA）。在U937，HCT-116，PC3，MCF-7，A549，К562，NCI-H929，Jurkat，THP-1，RPMI8228肿瘤细胞系和HEF细胞系上进行了抗肿瘤研究。发现所有合成的化合物对所述肿瘤细胞系具有比PPA更好的功效。化合物6（IC 50  = 0.59±0.27μM）被观察到11倍的活性比PPA（IC 50  = 6.5±0.30μM）朝向所述NCI-H929细胞系，与18的化合物的治疗指数6被确定为对NCI-H929（IC 50  = 0.9±0.05 µM）和A549（IC 50）的活性比依托泊苷高出一半以上，是其的16倍 = 100±7.0 µM）细胞系。
• Synthesis of natural phaeosphaeride A derivatives and an in vitro evaluation of their anti-cancer potential
  作者：Victoria V. Abzianidze、Daria S. Prokofieva、Leonid A. Chisty、Ksenia P. Bolshakova、Alexander O. Berestetskiy、Taras L. Panikorovskii、Alexander S. Bogachenkov、Alvin A. Holder

  DOI：10.1016/j.bmcl.2015.10.048

  日期：2015.12

  Derivatives of phaeosphaeride A (PPA) were synthesised and characterised; then anti-cancer studies were carried out on the A549 cancer cell line. It was found that the acetyl derivative (compound 3) displayed comparable in vitro cytotoxicity to that of PPA (EC50 = 49 ± 7 μM and EC50 = 46 ± 5 μM, respectively), while chloroacetyl derivative 6 (EC50 = 33 ± 7 μM) was found to have better efficacy towards

  合成了Phphasphaeride A（PPA）的衍生物并进行了表征；然后在A549癌细胞系上进行了抗癌研究。发现乙酰基衍生物（化合物3）具有与PPA相当的体外细胞毒性（分别为EC 50  = 49±7μM和EC 50  = 46±5μM），而氯乙酰基衍生物6（EC 50  = 33±发现7μM）对A549癌细胞系具有更好的功效。
• Antitumor activity of phaeosphaeride A modified with nitrogen heterocyclic groups
  作者：Sofya A. Zakharenkova、Victoria V. Abzianidze、Natalia I. Moiseeva、Diana S. Lukina、Leonid S. Chistyi、Denis V. Krivorotov、Yuri G. Trishin

  DOI：10.1016/j.mencom.2021.09.023

  日期：2021.9
• Synthesis of natural phaeosphaeride A and semi-natural phaeosphaeride B derivatives
  作者：Victoria V. Abzianidze、Ksenia P. Efimova、Ekaterina V. Poluektova、Yuri G. Trishin、Victor A. Kuznetsov

  DOI：10.1016/j.mencom.2017.09.020

  日期：2017.9

  6-O-Acylated phaeosphaeride A and phaeosphaeride B in reaction with secondary cyclic amines undergo stereospecific replacement of acyloxy group by pharmacophoric amino moiety. In case of chloroacetoxy derivative, chlorine displacement by such amines proceeds in the presence of triethylamine.