Synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′methylene-carbocyclic guanosine (FMCG)
AssigneeUniversity of Georgia Research Foundation, Inc.
InventorsChung K. Chu, Varughese Alexander Mulamootttil, Ram C. Mishra, Uma Sharan Singh
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Abstract
The invention provides a new convergent approach for the synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.
Claims3
A process for preparing the compound 2′-Fluoro-6′-Methylene-Carbocyclic Adenosine (FMCA) compound 10 from compound 8
- Comprising condensing an amine protected 6-amino purine compound according to the chemical structure:
- where P represents one or two amine protecting groups (preferably two BOC groups) onto compound 8 in the presence of triphenylphosphine and diisopropylazidocarboxylate (DIAD) in solvent to produce compound 8P
- where P represents one or two amine protecting groups;
- and
- subjecting compound 8P to deprotection to produce compound 10 (FMCA)
- wherein the synthesis is conducted in steps, wherein both compound 8P and 10 are separated and purified.
A process for preparing the compound 2′-Fluoro-6′-Methylene-Carbocyclic Adenosine (FMCA) compound 10 from compound 8
- Comprising condensing a di-Boc protected 6-amino purine compound according to the chemical structure:
- onto compound 8 in the presence of triphenylphosphine and diisopropylazidocarboxylate (DIAD) in solvent to produce compound 9
- subjecting compound 9 to deprotection to produce compound 10 (FMCA)
- wherein the synthesis is conducted in steps, wherein compounds 9 and 10 are separated and purified.
Any one or more of compounds 3, 4, 5, 6, 7, 8, 8P, 9, 9P or 9G hereof or a salt thereof.
Dependencies are inferred from the claim text.