Practical synthesis of (R)-(+)-6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4-hydroxyphenyl)hexanoic acid: a key intermediate for a therapeutic drug for neurodegenerative diseases

Itô, Tatsuya; Ikemoto, Tomomi; Yamano, Toru; Mizuno, Yukio; Tomimatsu, Kiminori

doi:10.1016/s0957-4166(03)00580-9

Cited by 18 publications

(20 citation statements)

References 10 publications

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“…Unfortunately, as in many other cases from the fine chemicals and pharmaceuticals sector the synthesis of these compounds is still based on stoichiometric reactions in the field of organic chemistry where often large amounts of waste are formed, even though cleaner alternatives have been reported. Therefore, the reduction of menadione ( 1 ) to menadiol ( 2 ) (Scheme , path A ) is still preferably employed by using inorganic reduction reagents such as sodium dithionite (Na 2 S 2 O 4 )3–5 or Zn‐ZnCl 2 ‐EtOH reagent6 while reports upon the catalytic hydrogenation of menadione ( 1 ) are scarce and not sufficiently detailed 7,8. On the other hand, menadiol diacetate ( 4 ) is usually synthesized by using acetic anhydride, in the presence of triethylamine and 4‐(dimethylamino)pyridine (DMAP) 4.…”

Section: Methodsmentioning

confidence: 99%

“…The organic layer was separated, washed with water (2×200 mL), and concentrated under reduced pressure. The residue was triturated with n ‐hexane (300 mL) and the resulting crystals were collected by filtration, washed with n ‐hexane (100 mL), and dried under reduced pressure to give menadiol as a pale purple crystalline powder (procedure in agree with Tomimatsu3). 1 H NMR (DMSO‐ d 6 ): δ=2.23 (s, 3 H), 6.58 (s, 1 H), 7.29–7.36 (m, 2 H), 7.95–8.01 (m, 2 H), 8.22 (s, 1 H), 9.33 (s, 1 H).…”

Section: Methodsmentioning

confidence: 99%

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One‐Pot Hydroacetylation of Menadione (Vitamin K₃) to Menadiol Diacetate (Vitamin K₄) by Heterogeneous Catalysis

et al. 2012

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Vitamin K 4 (menadiol diacetate, MDD) can be easily synthesized through cleaner and more efficient catalytic alternatives following the green chemistry principles. Ionic gold-based hydroxylated fluorides are active bi-functional catalysts for the one-pot hydroacetylation of menadione leading to MDD with 77% selectivity. Unprecedent results were obtained in the presence of oxide-fluoride catalysts by using a microwave-assisted hydrogentransfer (Meerwein-Ponndorf-Verley reaction) coupled with an acetylation approach, yielding very high selectivities for the target product (95%).

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

One‐Pot Hydroacetylation of Menadione (Vitamin K₃) to Menadiol Diacetate (Vitamin K₄) by Heterogeneous Catalysis

et al. 2012

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“…84 – 86 °C)18 1H NMR (CDCl 3 ): δ 3.95 (s, 6H); 6.69 (s, 2H), 7.50 (m, 2H); 8.20 (m, 2H). Following a modified procedure of Ito et al,24 to a flame-dried 50 mL round bottom flask was added 1,4-dimethoxynaphthalene (1.34 g, 7.12 mmol) dissolved in CH 2 Cl 2 (10.0 mL) and then cooled to 0 °C under Argon. Then TiCl 4 (1 M in CH 2 Cl 2 , 8.0 mL, 8.0 mmol) was added slowly at 0 °C followed by α,α-dichloromethyl methyl ether (0.71 mL, 8.0 mmol) at 0 °C.…”

Section: Methodsmentioning

confidence: 99%

Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)

Nyland

Luo²,

Kelley³

et al. 2010

J. Med. Chem.

101

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The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Ape1/Ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Ape1 can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Ape1 redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Ape1. Benzoquinone and naphthoquinone analogs of the Ape1-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Ape1 redox activity, and the most potent analogs inhibited tumor cell growth with IC 50 values in the 10-20 micromolar range.

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“…1,4-Dimethoxy-2-methylnaphthalene was synthesized from menadione in two steps (via the 1,4-dihydroxy-2-methylnaphthalene) as described previously (25). The annexin V FITC apoptosis kit was purchased from CloneTech.…”

Section: Methodsmentioning

confidence: 99%

Menadione-induced Reactive Oxygen Species Generation via Redox Cycling Promotes Apoptosis of Murine Pancreatic Acinar Cells

Criddle

Gillies

Baumgartner-Wilson

et al. 2006

Journal of Biological Chemistry

325

243

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Oxidative stress may be an important determinant of the severity of acute pancreatitis. One-electron reduction of oxidants generates reactive oxygen species (ROS) via redox cycling, whereas two-electron detoxification, e.g. by NAD(P)H:quinone oxidoreductase, does not. The actions of menadione on ROS production and cell fate were compared with those of a non-cycling analogue (2,4-dimethoxy-2-methylnaphthalene (DMN)) using real-time confocal microscopy of isolated perfused murine pancreatic acinar cells. Menadione generated ROS with a concomitant decrease of NAD(P)H, consistent with redox cycling. The elevation of ROS was prevented by the antioxidant N-acetyl-L-cysteine but not by the NADPH oxidase inhibitor diphenyliodonium. DMN produced no change in reactive oxygen species per se but significantly potentiated menadione-induced effects, probably via enhancement of one-electron reduction, since DMN was found to inhibit NAD(P)H:quinone oxidoreductase detoxification. Menadione caused apoptosis of pancreatic acinar cells that was significantly potentiated by DMN, whereas DMN alone had no effect. Furthermore, bile acid (taurolithocholic acid 3-sulfate)-induced caspase activation was also greatly increased by DMN, whereas DMN had no effect per se. These results suggest that acute generation of ROS by menadione occurs via redox cycling, the net effect of which is induction of apoptotic pancreatic acinar cell death. Two-electron detoxifying enzymes such as NAD(P)H:quinone oxidoreductase, which are elevated in pancreatitis, may provide protection against excessive ROS and exert an important role in determining acinar cell fate.

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Practical synthesis of (R)-(+)-6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4-hydroxyphenyl)hexanoic acid: a key intermediate for a therapeutic drug for neurodegenerative diseases

Cited by 18 publications

References 10 publications

One‐Pot Hydroacetylation of Menadione (Vitamin K₃) to Menadiol Diacetate (Vitamin K₄) by Heterogeneous Catalysis

One‐Pot Hydroacetylation of Menadione (Vitamin K₃) to Menadiol Diacetate (Vitamin K₄) by Heterogeneous Catalysis

Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)

Menadione-induced Reactive Oxygen Species Generation via Redox Cycling Promotes Apoptosis of Murine Pancreatic Acinar Cells

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Practical synthesis of (R)-(+)-6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4-hydroxyphenyl)hexanoic acid: a key intermediate for a therapeutic drug for neurodegenerative diseases

Cited by 18 publications

References 10 publications

One‐Pot Hydroacetylation of Menadione (Vitamin K3) to Menadiol Diacetate (Vitamin K4) by Heterogeneous Catalysis

One‐Pot Hydroacetylation of Menadione (Vitamin K3) to Menadiol Diacetate (Vitamin K4) by Heterogeneous Catalysis

Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)

Menadione-induced Reactive Oxygen Species Generation via Redox Cycling Promotes Apoptosis of Murine Pancreatic Acinar Cells

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One‐Pot Hydroacetylation of Menadione (Vitamin K₃) to Menadiol Diacetate (Vitamin K₄) by Heterogeneous Catalysis

One‐Pot Hydroacetylation of Menadione (Vitamin K₃) to Menadiol Diacetate (Vitamin K₄) by Heterogeneous Catalysis