合成路线:Synthesis of intermediate (VI):2) The reaction of 5,8-dimethoxy-2-tetralone (I) with KCN and ammonium carbonate in refluxing ethanol gives 2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoic acid (II),which is acetilated with acetic anhydride to give 2-acetylamino-1,2,3,4-tetrahydro-2-naphthoic acid (XV),which is submitted to optical resolution with I-alpha-phenylethylamine yielding the 2(R) isomer (XVI).Esterification of (XVI) with methanol-H2SO4 affords the corresponding methyl ester (XVII),which by reaction first with NaH and DMSO and then with Al-Hg in THF is converted into the acetyl derivative (VI).
合成路线:Synthesis of intermediate (VI):1) The reaction of 5,8-dimethoxy-2-tetralone (I) with KCN and ammonium carbonate in refluxing ethanol gives 2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoic acid (II),which is esterified with methanol-HCl to the corresponding methyl ester (III).The optical resolution of (III) with D-(-)-mandelic acid affords the 2R isomer (IV),which by reaction first with NaH and DMSO and then with Zn and NaOH in water gives (R)-2-acetyl-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (V).The acetylation of (V) with acetic anhydride in pyridine yields (R)-2-acetyl-2-acetamido-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (VI).
合成路线:(R)-2-acetyl-2-acetamido-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (VI) is submitted to a Friedel-Crafts cyclocondensation with phthalic anhydride (VII) by means of anhydrous AlCl3 at 135 C to afford (R)-9-acetyl-9-acetamido-6,11-dihydroxy-7,8,9,10-tetrahydronaphthacene-5,12-dione (VIII).The protection of the acetyl group of (VIII) with ethylene glycol and p-toluenesulfonic acid gives the corresponding ketal (IX),which by cyclization with 1,3-dibromo-5,5-dimethylhydantoin (DDH) yields the pentacyclic oxazine (X).The hydrolysis of (X) with hot H2SO4 affords 9-amino-4-demethoxy-9-deoxydaunomycinone (XI),which is condensed with 3,4-di-O-acetyl-2-deoxy-beta-D-ribopyranosyl bromide (XII) (obtained from acetyl 3,4-di-O-acetyl-2-deoxy-beta-D-ribopyranoside (XIII) and trimethylsilyl bromide) by means of tetramethylurea in chloroform to give the 3',4'- di-O-acetyl derivative (XIV) of the desired product.Finally,this compound is deprotected by hydrolysis with anhydrous K2CO3 in methanol - dichloroethane.
参考文献标题:Stereospecific total synthesis of 9-aminoanthracyclines: (+)-9-Amino-9-deoxydaunomycin and related compounds
文献作者:Ishizumi,K.; et al.
参考来源:J Org Chem 1987,52(20),4477-85
合成路线:Synthesis of intermediate (VI):2) The reaction of 5,8-dimethoxy-2-tetralone (I) with KCN and ammonium carbonate in refluxing ethanol gives 2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoic acid (II),which is acetilated with acetic anhydride to give 2-acetylamino-1,2,3,4-tetrahydro-2-naphthoic acid (XV),which is submitted to optical resolution with I-alpha-phenylethylamine yielding the 2(R) isomer (XVI).Esterification of (XVI) with methanol-H2SO4 affords the corresponding methyl ester (XVII),which by reaction first with NaH and DMSO and then with Al-Hg in THF is converted into the acetyl derivative (VI).
合成路线:Synthesis of intermediate (VI):1) The reaction of 5,8-dimethoxy-2-tetralone (I) with KCN and ammonium carbonate in refluxing ethanol gives 2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoic acid (II),which is esterified with methanol-HCl to the corresponding methyl ester (III).The optical resolution of (III) with D-(-)-mandelic acid affords the 2R isomer (IV),which by reaction first with NaH and DMSO and then with Zn and NaOH in water gives (R)-2-acetyl-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (V).The acetylation of (V) with acetic anhydride in pyridine yields (R)-2-acetyl-2-acetamido-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (VI).
合成路线:(R)-2-acetyl-2-acetamido-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (VI) is submitted to a Friedel-Crafts cyclocondensation with phthalic anhydride (VII) by means of anhydrous AlCl3 at 135 C to afford (R)-9-acetyl-9-acetamido-6,11-dihydroxy-7,8,9,10-tetrahydronaphthacene-5,12-dione (VIII).The protection of the acetyl group of (VIII) with ethylene glycol and p-toluenesulfonic acid gives the corresponding ketal (IX),which by cyclization with 1,3-dibromo-5,5-dimethylhydantoin (DDH) yields the pentacyclic oxazine (X).The hydrolysis of (X) with hot H2SO4 affords 9-amino-4-demethoxy-9-deoxydaunomycinone (XI),which is condensed with 3,4-di-O-acetyl-2-deoxy-beta-D-ribopyranosyl bromide (XII) (obtained from acetyl 3,4-di-O-acetyl-2-deoxy-beta-D-ribopyranoside (XIII) and trimethylsilyl bromide) by means of tetramethylurea in chloroform to give the 3',4'- di-O-acetyl derivative (XIV) of the desired product.Finally,this compound is deprotected by hydrolysis with anhydrous K2CO3 in methanol - dichloroethane.
参考文献标题:SM-5887
文献作者:Hoshi,A.; Prous,J.; Castar,J.
参考来源:Drugs Fut 1988,13(11),962
产品链接: CAS No. 92395-36-3›› 产品链接: CAS No.110267-81-7››