合成路线:The reaction of racemic 4-demethoxydaunomycinone (I) with Br2 followed by hydrolysis in basic medium gives 4-demethoxyadriamycinone (II),which is treated with tert-butyldimethylsilyl chloride and imidazole in DMF to yield the monoprotected compound (III).The condensation of (III) with 3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-mannopyranose (IV) by means of N-iodosuccinimide (NIS),followed by chromatographic separation of the diastereomers affords (7S,9S)-14-O-(tert-butyldimethylsilyl)-4-demethoxy-7-O-(3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-mannopyranosyl)adriamycinone (V).The hydrolysis of (V) with sodium methoxide in methanol gives the silylated compound (VI),which is finally desilylated with tetrabutylammonium fluoride (TBAF) in dichloromethane/THF/pyridine.
参考文献标题:Synthesis of antitumor-active (7S,9S)-4-demethoxy-7-O-(2,6-dideoxy-2-iodo-alpha-L-mannopyranosyl) adriamycinone: Preparative resolution of a racemic anthracyclinone by alkoxyhalogenation of a glycal
文献作者:Horton,D.; Priebe,W.; Varela,O.
参考来源:Carbohydr Res 1984,130C1-3
合成路线:The reaction of racemic 4-demethoxydaunomycinone (I) with Br2 followed by hydrolysis in basic medium gives 4-demethoxyadriamycinone (II),which is treated with tert-butyldimethylsilyl chloride and imidazole in DMF to yield the monoprotected compound (III).The condensation of (III) with 3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-mannopyranose (IV) by means of N-iodosuccinimide (NIS),followed by chromatographic separation of the diastereomers affords (7S,9S)-14-O-(tert-butyldimethylsilyl)-4-demethoxy-7-O-(3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-mannopyranosyl)adriamycinone (V).The hydrolysis of (V) with sodium methoxide in methanol gives the silylated compound (VI),which is finally desilylated with tetrabutylammonium fluoride (TBAF) in dichloromethane/THF/pyridine.
参考文献标题:Annamycin
文献作者:Graul,A.; Prous,J.; Castar,J.
参考来源:Drugs Fut 1997,22(9),948
合成路线:The Diels-Alder cyclization of butadiene (VII) with 1,4-benzoquinone (VIII) in THF gives the naphthalenetrione (IX),which is acylated with acetic anhydride and TEA to yield the tetralone derivative (X).The Grignard reaction of (X) with vinylmagnesium bromide (XI) and CeCl3,followed by acylation with acetic anhydride,affords the tetraline derivative (XII),which is treated with NaBH4 and oxidized with cerium ammonium nitrate to provide the tetrahydronaphthoquinone (XIII).The cyclization of (XIII) with 4-acetoxy-3,4-dihydro-1H-2-benzopyran-1,3-dione (XIV) by means of NaH in THF gives the intermediate (XV),which rearranges to the tetracyclic dione (XVI).The palladium-catalyzed (PdCl2(MeCN)2) rearrangement of (XVI) in toluene yields the allyl acetate derivative (XVII),which is oxidized with peracetic acid and RuCl3 in water/acetonitrile/dichloromethane to afford the protected intermediate (XVIII).Finally,this compound is deprotected and simultaneously epimerized by a treatment with HCl in refluxing isopropanol/water to provide the desired target intermediate (II).
参考文献标题:Synthesis of 4-demethoxyadriamycinone utilizing ruthenium-catalyzed oxidation of allyl acetates
文献作者:Hottop,T.; et al.
参考来源:Tetrahedron Lett 2001,42(19),3343
产品链接: CAS No. 92689-49-1››