Composition comprising naphthoquinone-based compound as active ingredient, for preventing or ameliorating fatigue, cachexia, pain, cognitive decline and hematopoietic stem cell reduction which are side effects related to anticancer drug treatment
A hematopoietic stem cell, anticancer drug technology for preventing or ameliorating fatigue, cachexia, pain, cognitive decline and hematopoietic stem cells as side effects associated with anticancer drug treatment containing a naphthoquinone-based compound as an active ingredient Field of reduced compositions capable of addressing problems such as cognitive decline and hematopoietic stem cell reduction effects or effects
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Embodiment 1
[0288] Embodiment 1: the synthesis of β-lapachone
[0289] Since the amount of β-lapachone obtained from lapacho trees is relatively small, a considerable amount of lapaol, which is the raw material for the synthesis of β-lapachone, can be obtained from lapacho trees. Thus, a method for synthesizing β-lapachone using lapachol has been developed long ago. That is, if Lappaol and sulfuric acid are mixed together and vigorously stirred at room temperature, β-Lappaquinone can be obtained in relatively high yield.
[0290] In a preferred embodiment of the present invention, to obtain Lappaol, 2-hydroxy-1,4-naphthoquinone (17.4g, 0.10M) was dissolved in DMSO (120ml) and LiH (0.88g, 0.11M) was added slowly ). At this time, care is required because hydrogen is generated. The reaction solution was stirred. After confirming that hydrogen gas was no longer generated, the reaction solution was continued to be stirred for 30 minutes. Then, prenyl bromide (1-bromo-3-methyl-2-butene, ...
Embodiment 2
[0296] Embodiment 2: Synthesis of Dongnidone
[0297] In the process of obtaining Lappaol in Example 1, the isolated solid that was not dissolved in EtOAc was O-substituted 2-prenyloxy-1,4-naphthoquinone (O-alylated 2-prenyloxy -1,4-maphthoquinone), which is different from C-substituted lapachol (C-alylated lapachol). The solid was purified again by recrystallization from EtOAc. Next, the purified solid (3.65 g, 0.015 M) was dissolved in toluene and refluxed for 5 hours in order to induce Claisen rearrangement. Toluene was concentrated by distillation under reduced pressure, and the resulting mixture was stirred vigorously at room temperature for 10 minutes while mixing with sulfuric acid (15 ml) without further purification, and then ice (100 g) was added to terminate the reaction.
[0298] CH is added to the reactant 2 Cl 2 (50ml), with vigorous stirring, the isolated CH 2 Cl 2 layer. Separate the layers with 5% NaHCO 3 washing. The aqueous layer was again washed ...
Embodiment 3
[0300] Embodiment 3: Synthesis of α-Dongnidone
[0301]2-prenyloxy-1,4-naphthoquinone (2-prenyloxy-1,4-maphthoquinone) (4.8 g, 0.020 M) (4.8 g, 0.020 M) purified in Example 2 was dissolved in xylene, then refluxed for 15 hours in order to induce Claisen rearrangement at a higher temperature and longer time than in Example 1. During the process, α-donidone is obtained in a state of proceeding to the cyclization reaction, and a lapacol derivative in which one of the two methyl groups has been rearranged. Xylene was then concentrated by distillation under reduced pressure, followed by silica gel chromatography. As a result, pure α-donidone (1.65 g) was obtained.
[0302] 1H-NMR (CDCl3, δ): 8.06 (1H, d, J = 8Hz), 7.64 (2H, m), 7.57 (1H, m), 3.21 (1H, q, J = 7Hz), 1.53 (3H, s ), 1.51(3H, s) 1.28(3H, d, J=7Hz).
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