- A method for synthesizing ammonia supple ratio star
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The invention discloses a synthetic method for amrubicin. R-2-acetyl-2-acetamido-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene is used as a raw material, and is subjected to acylation and cyclization with phthalic anhydride. 1,3-propanediol and derivatives thereof are used to protect carbonyl, and the protective group is liable to remove in a hydrolysis reaction. The amrubicin is prepared by a step of subjecting (+)-9-amino-4-demethoxy-9-deoxy-daunomycinone with 2-deoxy-3,4-di-O-acetyl-beta-D-erythro-pentapyranosyl-1,1,1-trichloroiminoacetate to a nucleoside-forming reaction to obtain (+)-9-amino-4-demethoxy-9-deoxy-7-O-(2-deoxy-3,4-di-O-acteyl-beta-D-erythro-pentapyranosyl) daunomycinone, and a step of removing acetyl. The synthetic method can avoid generation of isomers during a hydrolysis process effectively. The synthetic method has simple subsequent purification steps. The nucleoside-forming reaction can decrease the production cost effectively. The synthetic method is suitable for industrial applications.
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- Stereospecific Total Synthesis of 9-Aminoanthracyclines: (+)-9-Amino-9-deoxydaunomycin and Related Compounds
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9-amino-9-deoxydaunomycin and related compounds, in which the hydroxyl group at the 9-position of daunomycin is replaced by an amino group, have been synthesized.Asymmetry was introduced into the synthetic sequence for the AB synthon by resolution of the intermediate amino ester or acetamido acid to afford (R)-(-)-2-acetyl-2-acetamido-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene, which was converted to the tetracyclic amido ketones by Friedel-Crafts acylation with phthalic anhydride or its 3-methoxy derivative.The resulting regioisomers 4- and 1-methoxy compounds were separed, after methylation and selective demethylation, by crystallization and preparative TLC.The required introduction of the C7-hydroxyl function proceeded stereosepcifically via a three-step reaction sequence involving formation of an oxazine compound.The silver trifluoromethane assisted glycosidation of the resulting aglycons with 2-deoxy-3,4-di-O-acetyl-D-erythro-pentopyranosyl bromide or N,O-bis(trifluoroacetyl)daunosaminyl chloride, followed by alkaline hydrolysis afforded the target glycosides.The work reported herein comprises an efficient, practical synthesis of 9-amino-9-deoxydaunomycin and its analogues with the same stereochemistry as in the naturally occurring anthracyclines.
- Ishizumi, Kikuo,Ohashi, Naohito,Tanno, Norihiko
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p. 4477 - 4485
(2007/10/02)
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- Aminonaphthacene derivatives
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9-Aminonaphthacene derivative having the formula: STR1 wherein R1 and R2 are both hydrogen atoms or either one of them is a hydrogen atom and the other is hydroxy group or methoxy group; R3 is acetyl group or 1-hydroxyethyl group; R4 is a hydrogen atom; R5 is a hydrogen atom, hydroxy group, lower alkanoyloxy group, amino group, halogen-substituted lower alkanoylamino group or morpholino group; R6 is a hydrogen atom, hydroxy group, lower alkanoyloxy group or tetrahydropyranyloxy group; R7 is a hydrogen atom or methyl group; R is a hydrogen atom; and n is zero or one, which is useful as anti-cancer chemical agents with lower toxicity and with little local irritation and is able to orally be applied.
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