Processes for preparing substituted 1, 3-oxathiolanes with antiviral properties
AssigneeBioChem Pharma Inc.
InventorsBernard Belleau, Tarek Mansour, Allan Tse, Colleen A. Evans, Haolun Jin, Boulos Zacharie, Nghe Nguyen-Ba
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Abstract
Disclosed are processes for preparing compounds of the formula (I) and pharmaceutically acceptable salts or esters thereof: 1 wherein R2 is a purine or pyrimidine base or an analogue or derivative thereof; and Z is S, S═O or SO2. The invention also relates to intermediates of use in the preparation of these compounds.
Claims34
A process for preparing an oxathiolane of formula (I), pharmaceutically acceptable salts or esters, and geometric and optical isomers thereof:
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- wherein:
- R2 is a purine or pyrimidine base or an analogue or derivative thereof;
- and Z is S, S═O or SO2;
- the process comprising the step of reacting a mercaptoacetaldehyde with a compound having formula RwOCH2CHO, wherein Rw is hydrogen or a hydroxyl protecting group R1,
- under neutral or basic conditions to obtain an intermediate of formula (III):
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A process for preparing an oxathiolane of formula (I), pharmaceutically acceptable salts or esters, and geometric isomers thereof, and mixtures of those isomers:
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- wherein:
- R2 is a purine or pyrimidine base or an analogue or derivative thereof;
- and
- Z is selected from a group consisting of S, S═O and SO2;
- the process comprising the step of reacting a mercaptoacetaldehyde with a compound having formula RyOOCCHO, wherein Ry is substituted or unsubstituted C1-12 alkyl or substituted or unsubstituted C6-20 aryl to obtain an intermediate of formula (XV):
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Intermediates useful for the production of oxathiolane compounds, said intermediates selected from the group consisting of:
- trans-2-hydroxymethyl-5-acetoxy-1,3-oxathiolane;
- cis-2-benzoyloxymethyl-5-hydroxy-1,3-oxathiolane, trans-2-benzoyloxymethyl-5-hydroxy-1,3-oxathiolane and mixtures thereof;
- cis-2-benzoyloxymethyl-5-(4′,5′-dichlorobenzoyloxy)-1,3-oxathiolane, trans-2-benzoyloxymethyl-5-(4′,5′-dichlorobenzoyloxy)-1,3-oxathiolane and mixtures thereof;
- cis-2-benzoyloxymethyl-5-trimethylacetoxy-1,3-oxathiolane, trans-2-benzoyloxymethyl-5-trimethylacetoxy-1,3-oxathiolane and mixtures thereof;
- cis-2-benzoyloxymethyl-5-(2′,2′,2′-trichloroethoxycarbonyloxy)1,3-oxathiolane, trans-2-benzoyloxymethyl-5-(2′,2′,2′-trichloroethoxy carbonyloxy)1,3-oxathiolane and mixtures thereof;
- cis-2-benzoyloxymethyl-5-ethoxycarbonyloxy)-1,3-oxathiolane, trans-2-benzoyloxymethyl-5-ethoxycarbonyloxy-1,3-oxathiolane and mixtures thereof;
- cis-2-benzoyloxymethyl-5-methoxycarbonyloxy-1,3-oxathiolane, trans-2-benzoyloxymethyl-5-methoxycarbonyloxy-1,3-oxathiolane and mixtures thereof;
- cis2-benzoyloxymethyl-5-acetoxy-1,3-oxathiolane, trans-2-benzoyloxymethyl-5-acetoxy-1,3-oxathiolane and mixtures thereof;
- cis-2-benzoyloxymethyl-5-(N4′-acetylcytosin-1′-yl)-1,3-oxathiolane, trans-2-benzoyloxymethyl-5-(N4′-acetylcytosin-1′-yl)-1,3-oxathiolane and mixtures thereof;
- cis-2-benzoyloxymethyl-5-(cytosin-1′-yl)-1,3-oxathiolane, trans-2-benzoyloxymethyl-5-(cytosin-1′-yl)-1,3-oxathiolane and mixtures thereof;
- cis-2-carboethoxy-5-hydroxy-1,3-oxathiolane, trans-2-carboethoxy-5-hydroxy-1,3-oxathiolane and mixtures thereof;
- cis-2-carboethoxy-5-methoxycarbonyloxy-1,3-oxathiolane, trans-2-carboethoxy-5-methoxycarbonyloxy-1,3-oxathiolane and mixtures thereof;
- cis-2-carboethoxy-5-acetoxy-1,3-oxathiolane, trans-2-carboethoxy-5-acetoxy-1,3-oxathiolane and mixtures thereof;
- cis-2-carboethoxy-5-(N4′-acetylcytosin-1′-yl)-1,3-oxathiolane;
- cis-2-carboethoxy-5-(cytosin-1′-yl)-1,3-oxathiolane;
- cis-2-carboethoxy-5-(uracil-1′-yl)-1,3-oxathiolane;
- cis-2-benzoyloxymethyl-5-(cytosin-1′-yl)-1,3-oxathiolane;
- cis-ethyl-5-iodo-1,3-oxathiolan-2-carboxylate, trans-ethyl-5-iodo-1,3-oxathiolan-2-carboxylate and mixtures thereof;
- cis-ethyl-5-(6′-chloropurin-9′-yl)-1,3-oxathiolan-2-carboxylate, trans-ethyl-5-(6′-chloropurin-9′-yl)-1,3-oxathiolan-2-carboxylate and mixtures thereof;
- and
- cis-ethyl-5-(6′-chloropurin-7′-yl)-1,3-oxathiolan-2-carbonate, trans-ethyl-5-(6′-chloropurin-7′-yl)-1,3-oxathiolan-2 carboxylate and mixtures thereof.
Dependencies are inferred from the claim text.