Novel spiro-1,2,4-trioxanes
AssigneeCouncil of Scientific and Industrial Research
InventorsChandan Singh, Heetika Malik, Sunil Puri
Life of this patent
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Abstract
The present invention relates to spiro 1,2,4-trioxanes of general formula 4. This invention more particularly relates to a process for the preparation of a series of spiro 1,2,4-trioxanes. Wherein, Ar represents aryl groups such as phenyl, 4-biphenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-methylphenyl, 4-cyclohexylphenyl, 1-naphthyl, 2-naphthyl and the like and R represents hydrogen or the alkyl group such as methyl, ethyl and the like. Several of these compounds show high order of antimalarial activity against multidrug-resistant malaria in mice and thus hold promise as antimalarial agents against multidrug-resistant malaria.
Claims29
A spirol,2,4-trioxane of general formula 4,
- wherein, Ar represents an aryl groups, and R represents hydrogen or an alkyl group.
A process for the preparation of a spiro 1,2,4-trioxane of general formula 4 comprising the steps of:
- a) photooxygenating of allylic alcohols of formula 1 in presence of a sensitizer and a light source which provides visible light, in an organic solvent at temperature ranging from −10° C. to 0° C. to obtain β-hydroxyhydroperoxide of formula 2,
- b) reacting β-hydroxyhydroperoxide of formula 2 in-situ with 1,4-cyclohexanedione in the presence of an acid catalyst at temperature 0° C. to for 18 hours to obtain keto trioxanes of general formula 3,
- c) reacting the keto trioxanes of step (b) with triethylphosphonoacetate or substituted triethylphosphonoacetate in the presence of a base in an organic solvent at a temperature ranging from 0° C. to 50° C. to obtain spiro 1,2,4-trioxanes of formula 4,
- d) isolating and purifying by conventional methods to furnish a spiro 1,2,4-trioxane of formula 4.
A method of treating a subject having malaria, comprising administering to the subject a pharmaceutically effective amount of a composition comprising a compound of formula 4,
- Wherein, Ar represents an aryl group selected from phenyl, 4-biphenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-methylphenyl, 4-cyclohexylphenyl, 1-naphthyl, 2-naphthyl;
- R represents hydrogen or an alkyl group, and pharmaceutical acceptable salts thereof.
Dependencies are inferred from the claim text.