Title:
NOVEL ANTHRACYCLINE GLYCOSIDE AND ITS MANUFACTURE
Document Type and Number:
Japanese Patent JPS5661400
Kind Code:
A
Abstract:
Anthracycline glycosides of formula (I), and the process for their prepn. are new, (where X is H or OH; R1 is H, alkyl or aryl; R2 is H or trifluoroacetyl). (I) are antimitotic agents, useful in the treatment of tumours. 8-Methoxy daunorubicin, 8-methoxy doxorubicin, are claimed. Daunomycinone (II) is refluxed in chloroform with 2,2-dimethoxy propane in the presence of para toluene sulphonic acid (PTSA) to give spiro (7,8-anhydro-9-deacetyl-9-deoxy daunomycinone-2',2'- dimethyl-5'-methyl -5'-methoxy dioxolane) (III). Epoxidation of (III) in chloroform, followed by benzylation (benzyl bromide) gives sprio(6,11-dibenzyl-7,8-epoxy-9-deacetyl-9-deoxy daunomycinone-9,4'-2',2'-dimethyl-5'-methyl-5-methoxy dioxolane) (IV) The oxirane ring is opened by treatment with methanol and PTSA, opt. alkylated, and the dioxolane ring and benzyl gps. hydrolysed by treatment with trifluoroacetic acid at 0 deg. C. to give (V). (V) is hydrolysed with trifluoroacetic acid at ambient temperature, and condensed with 1-chloro-N,O-ditrifluoroacetyl daunosame daunosamine (VI) in an organic solvent in the presence of the Ag salt of trifluoromethane sulphonic acid to give the corresp. N,O-protected glycosides. The trifluoroacetyl protecting groups are eliminated by treatment with methanol to give (I;R2 is trifluoroacetyl; X is H). The trifluoroacetyl gp. may be removed by mild alkaline hydrolysis using 0.1N NaOH. (I;X is OH) is prepd. from this by bromination and hydrolysis with Na formate.
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Inventors:
FURANCHIESUKO ANJIERUTSUCHI
SERUJIO PENKO
FUEDERIKO ARUKAMONE
OORERIO DEI MARUKO
SERUJIO PENKO
FUEDERIKO ARUKAMONE
OORERIO DEI MARUKO
Application Number:
JP13997680A
Publication Date:
May 26, 1981
Filing Date:
October 08, 1980
Export Citation:
Assignee:
ERBA CARLO SPA
International Classes:
A61K31/70; A61K31/7028; A61K31/7034; A61K31/704; A61P35/00; C07D317/72; C07D319/14; C07D493/10; C07H15/252; (IPC1-7): A61K31/70; C07D317/72; C07D319/14; C07H15/24