e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Synthesis of Shikalkin (±Shikonin) and Related Compounds

…, Y Tanoue, A Hatada, H Sakamoto

Index: Terada; Tanoue; Hatada; Sakamoto Bulletin of the Chemical Society of Japan, 1987 , vol. 60, # 1 p. 205 - 213

Full Text: HTML

Citation Number: 75

Abstract

The key intermediate, 2-formyl-1, 4, 5, 8-tetramethoxynaphthalene, was prepared through 1, 4, 5, 8-tetramethoxynaphthalene, which was obtained from 1, 5-naphthalenediol via three steps or from naphthazarin via one step. A total synthesis of shikalkin and dihydroshikalkin have been accomplished with this aldehyde via a side-chain introductions with Grignard reactions and the following demethylations.

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

~%

2-(1-hydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1-hydroxy-4-...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

2-(1-hydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1-hydroxy-4-...

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

~%

2-(1-hydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1-hydroxy-4-...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

~%

2-(1-hydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1-hydroxy-4-...

Naphthalene,1,5-dimethoxy- Structure

Naphthalene,1,5...

~%

2-(1-hydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1-hydroxy-4-...

2-(1-hydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1-hydroxy-4-...

~25%

5,8-dihydroxy-2-(4-methylpentyl)naphthalene-1,4-dione Structure

5,8-dihydroxy-2...

5,8-dihydroxy-2-(1-hydroxy-4-methylpentyl)-1,4-naphthoquinone Structure

5,8-dihydroxy-2...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

~%

5,8-dihydroxy-2-(4-methylpentyl)naphthalene-1,4-dione Structure

5,8-dihydroxy-2...

Naphthalene,1,5-dimethoxy- Structure

Naphthalene,1,5...

~%

5,8-dihydroxy-2-(4-methylpentyl)naphthalene-1,4-dione Structure

5,8-dihydroxy-2...

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

~%

5,8-dihydroxy-2-(4-methylpentyl)naphthalene-1,4-dione Structure

5,8-dihydroxy-2...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

5,8-dihydroxy-2-(4-methylpentyl)naphthalene-1,4-dione Structure

5,8-dihydroxy-2...

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

~%

5,8-dihydroxy-2-(4-methylpentyl)naphthalene-1,4-dione Structure

5,8-dihydroxy-2...

2-(1-hydroxy-4-methylpentyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(1-hydroxy-4-...

~%

5,8-dihydroxy-2-(4-methylpentyl)naphthalene-1,4-dione Structure

5,8-dihydroxy-2...

METHYLMAGNESIUM IODIDE Structure

METHYLMAGNESIUM...

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

~86%

4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentane-1,4-diol Structure

4-methyl-1-(1,4...

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

~%

4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentane-1,4-diol Structure

4-methyl-1-(1,4...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentane-1,4-diol Structure

4-methyl-1-(1,4...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

~%

4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentane-1,4-diol Structure

4-methyl-1-(1,4...

Naphthalene,1,5-dimethoxy- Structure

Naphthalene,1,5...

~%

4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentane-1,4-diol Structure

4-methyl-1-(1,4...

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

~%

4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentane-1,4-diol Structure

4-methyl-1-(1,4...

2-(4,4-(ethylenedioxy)-1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(4,4-(ethylen...

~%

4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentane-1,4-diol Structure

4-methyl-1-(1,4...

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

Naphthalene,1,5-dimethoxy- Structure

Naphthalene,1,5...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

2-(4,4-(ethylenedioxy)-1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(4,4-(ethylen...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dimethoxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

~27%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

4-methyl-1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentane-1,4-diol Structure

4-methyl-1-(1,4...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

Naphthalene,1,5-dimethoxy- Structure

Naphthalene,1,5...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

2-(4,4-(ethylenedioxy)-1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(4,4-(ethylen...

~%

2-(1,4-dihydroxy-4-methylpentyl)-5,8-dihydroxynaphthalene-1,4-dione Structure

2-(1,4-dihydrox...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

Dimethyl sulfate Structure

Dimethyl sulfate

~46%

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

Dimethyl sulfate Structure

Dimethyl sulfate

Naphthazarin Structure

~%

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

2-(4,4-(ethylenedioxy)-1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(4,4-(ethylen...

~87%

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

~%

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

Naphthalene,1,5-dimethoxy- Structure

Naphthalene,1,5...

~%

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

~%

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

~%

5-hydroxy-5-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-2-one Structure

5-hydroxy-5-(1,...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

Naphthazarin Structure

2-(1-methoxy-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(1-methoxy-4-...

~4%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

~%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

1,4,5,8-tetramethoxynaphthalene Structure

1,4,5,8-tetrame...

~%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

~%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

Naphthalene,1,5-dimethoxy- Structure

Naphthalene,1,5...

~%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

2-(4-hydroxy-1-methoxy-4-methylpentyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(4-hydroxy-1-...

~%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

2-(1-methoxy-4-oxopentyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(1-methoxy-4-...

~%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

2-(4,4-(ethylenedioxy)-1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene Structure

2-(4,4-(ethylen...

~%

naphthazarin-dimethyl-hydrofuran hdfr Structure

naphthazarin-di...

1,5-dibromo-4,8-dimethoxynaphthalene Structure

1,5-dibromo-4,8...

~%

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

1,4-Naphthalenedione,5,8-dimethoxy- Structure

1,4-Naphthalene...

~%

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

Naphthalene,1,5-dimethoxy- Structure

Naphthalene,1,5...

~%

2-SULFO-1,4-BENZENEDICARBOXYLIC ACID 1,4-DIMETHYL ESTER, SODIUM SALT Structure

2-SULFO-1,4-BEN...

Total synthesis of shikalkin [(±)-shikonin]

[Terada, Akira; Tanoue, Yasuhiro; Hatada, Akira; Sakamoto, Hiroshi Journal of the Chemical Society, Chemical Communications, 1983 , # 18 p. 987 - 988]

Total synthesis of shikalkin [(±)-shikonin]

[Terada, Akira; Tanoue, Yasuhiro; Hatada, Akira; Sakamoto, Hiroshi Journal of the Chemical Society, Chemical Communications, 1983 , # 18 p. 987 - 988]