54952-43-1Relevant articles and documents
An improved and practical synthesis route to antiproliferative (±)-shikonin and its O-acyl derivatives
Ono, Mana,Abe, Shouki,Higai, Koji,Higashi, Shoko,Saito, Setsuo,Saito, Ryota
, p. 738 - 746 (2020/12/09)
Shikonin and its O-acyl derivatives are attracting increasing levels of attention among medicinal chemists due to their potencies as highly selective cytotoxic agents against cancer cells. However, providing a large number of shikonin-related samples by organic synthesis remains challenging. In the present study, we developed an improved and practical synthesis route to shikonin derivatives by olefin metathesis that has enabled the gram-scale preparation of a prenylated tetramethylnaphthazaline, a key intermediate in the synthesis of shikonin. In addition, a method for the selective cleavage of the acyl protecting groups at the phenolic positions of tri-O-acylated shikonins has been developed that provides concise routes to diverse O-acylshikonin derivatives.
High performance liquid chromatography resolution method of alkannin raceme and naphthazarin parent nucleus hydroxyl methylated carbonyl oxime derivative of alkannin raceme
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Paragraph 0036-0045, (2021/04/17)
The invention discloses a high performance liquid chromatography resolution method of alkannin raceme and naphthazarin parent nucleus hydroxyl methylated carbonyl oxime derivatives thereof, which comprises the following steps: using high performance liquid chromatography, using amylose-tris [(S)-alpha-methyl benzyl carbamate] as a filler and an n-hexane-isopropanol mixed solvent as a mobile phase, separating high-purity R-(+)-alkannin from an alkannin raceme, separating high-purity S-(+)-alkannin naphthazarin parent nucleus hydroxyl methylated carbonyl oxime derivatives from an alkannin raceme naphthazarin parent nucleus hydroxyl methylated carbonyl oxime derivative, and combining a certain separation and purification means. Therefore, the production efficiency of R-(+)- alkannin is improved, and the efficiency of producing the optically pure alkannin naphthazarin parent nucleus hydroxyl methylated carbonyl oxime derivative by using an intermediate resolution method is improved.
An efficient multigram synthesis of alkannin and shikonin
Wang, Rubing,Zhou, Shanshan,Jiang, Hudagula,Zheng, Xiaogang,Zhou, Wen,Li, Shaoshun
, p. 1373 - 1379 (2012/04/04)
The concise and efficient total syntheses of alkannin (1) and shikonin (2), based on the resolution of a key acid intermediate, are achieved with excellent enantiomeric excesses and high overall yields (99 % ee, 15.6 % for 1 and 99.8 % ee, 11.9 % for 2). The key steps of the synthetic strategy involve the convenient synthesis and separation of a pair of amide diastereoisomers and the mild hydrolysis of the amide to remove the amine chiral auxiliary, together with an efficient deprotection sequence of the methyl protecting groups. The concise and efficient syntheses of alkannin and shikonin remained elusive until recently. We have developed a new method of resolution for achieving the syntheses of alkannin (1) and shikonin (2) in excellentenantiomeric excesses (≥ 99 % ee for 1 and ≥ 99.8 % ee for 2) and high yields (27.5 %) with low cost, which is practical for use in large-scale preparation. Copyright
Tigloylshikonin, a new minor shikonin derivative, from the roots and the commercial root extract of Lithospermum erythrorhizon
Ito, Yusai,Onobori, Kenichi,Yamazaki, Takeshi,Kawamura, Yoko
experimental part, p. 117 - 119 (2011/02/28)
Tigloylshikonin, a new shikonin derivative esterified with tiglic acid ((E)-2-methylbut-2-enoic acid), was isolated as a minor pigment from a food colorant "Shikon color," a commercial root extract from Lithospermum erythrorhizon SIEBOLD et ZUCCARINI. The structure of tigloylshikonin was elucidated using 1H, 13C, the difference nuclear Overhauser effect (NOE), and 2D NMR techniques. Its stereochemistry was determined by chiral-phase HPLC analysis. Tigloylshikonin was also found in the roots of L. erythrorhizon, which indicated that this new shikonin derivative is a typical component of naphthoquinone pigments in the roots of L. erythrorhizon.
An efficient improvement on total synthesis of shikonin
Rao, Zhen,Zhou, Wen,Peng, Ying,Li, Shao-Shun
experimental part, p. 236 - 237 (2010/08/06)
The problem associated with electrolytic deprotection, which is a concern in the total synthesis of shikonin, is solved by the addition of Cu2+ to the electrolysis system. The improvement has three advantages: first, it practically increased the yield from 40 to 85%; second, the isolation of shikonin became much easier. Third, the reaction time was significantly shortened.
A new efficient route for multigram asymmetric synthesis of alkannin and shikonin
Couladouros, Elias A.,Strongilos, Alexandros T.,Papageorgiou, Vassilios P.,Plyta, Zoi F.
, p. 1795 - 1803 (2007/10/03)
A short and convergent approach for the synthesis of alkannin, shikonin and shikalkin is presented. A Hauser-type annulation of cyanophthalide 26 with enone 7 affords the complete aromatic system in just one step with concomitant attachment of the entire side chain. Subsequent Corey's oxazaborolidine mediated asymmetric reduction of the above advanced intermediate, leads to the required isomer in high enantiomeric excess. Finally, a selective and high yielding deprotection protocol furnishes the title compounds as pure crystalline precipitates. Thus, a multigram synthesis of shikonin, alkannin and shikalkin is achieved in high yield and enantioselectivity.
Concise and efficient total syntheses of alkannin and shikonin
Nicolaou,Hepworth, David
, p. 839 - 841 (2007/10/03)
Two enantiomic natural products with wound-healing properties, alkannin (1) and shikonin (2), are accessible by a short and efficient total synthesis. The success was achieved by a novel protecting system for masking of 5,8-dihydroxy-1,4-naphthoquinones (naphthazarins) and a highly stereoselective ketone reduction.
Synthesis of dl-shikonin by vanadium(II)-assisted cross-coupling and electrooxidation of aromatic nuclei
Torii,Akiyama,Yamashita,Inokuchi
, p. 2917 - 2922 (2007/10/03)
Vanadium(II)-assisted cross-coupling of 1,4,5,8-tetramethoxynaphthalene-2-carbaldehyde and 3-methyl-2-butenal was employed for introduction of the side chain of dl-shikonin. 2-(1-Hydroxy-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxynaphthalene was prepared by the pinacol coupling and the subsequent palladium-catalyzed hydrogenolysis of the carbon-oxygen bond at the allylic position of the diol carbonate. Electrochemical oxidation of the 2-substituted 1,4,5,8-tetramethoxynaphthalene, followed by reductive acetylation with zinc and the subsequent electrooxidation of the resulting 5,8-diacetoxy-1,4-dimethoxynaphthalene, afforded the corresponding 5,8-diacetoxy-1,4-naphthoquinone, whose alkaline hydrolysis furnished dl-shikonin.
SYNTHESIS OF SHIKALKIN AND CERTAIN RALATED COMPOUNDS
Novikov, V. L.,Balaneva, N. N.,Moiseenkov, A. M.,Elyakov, G. B.
, p. 1485 - 1494 (2007/10/02)
A successful total synthesis of a biologically active pigment from plants of the Boraginaceae family was carried out with naphthazarine as the starting material, and using the 1,4,5,8-tetramethoxynaphthalene, the corresponding 2-vinyl derivative and its epoxide or a cyclopropane adduct with diazoacetic ester at the key stages.In the course of developing the scheme of the synthesis of shikalkin, its three analogs were obtained, differing in the nature of the monoterpenoid side chain. Keywords: shikonin, alkannin, shikalkin, naphthazarine, tetramethoxynaphthalene, olefinization according to Wittig, cyclopropyl-carbinylic rearrangement, cerium-ammonium nitrate.
