Substituted 1,3-Oxathiolanes with Antiviral Properties

Patent Substituted 1,3-Oxathiolanes with Antiviral Properties 

Mansour etal, US Patent 6,369,066 Assignee BioChem Pharma Inc. 

1-Benzoyl glycerol (50 g) dissolved in 500 ml CH2CI2 and 25 ml water was added portion-wise to NaI04 under vigorous stirring conditions at ambient temperature. The solution was stirred 2 hours, MgS04 (100 g) added, and the mixture stirred an additional 30 minutes. The mixture was filtered, the solution concentrated, and the residue distilled at 92-94 °C at 0.25 mm Hg to obtain 50 g of product. H-NMR data supplied. 

The product from Step 1 (6.21 g), 3 ml 2-mercaptoethanol and para-toluenesulfonic acid (0.2 g) were dissolved in 150 ml toluene and the mixture heated under Dean-Stark conditions 3 hours. The mixture was cooled, washed with 50 ml NaHCOj solution and 2.5 ml water, dried, and concentrated. The mixture was purified using chromatography on silica gel with hexane/EtOAc, 9 1, and the product isolated in 90% yield. H-NMR data supplied. 

The product mixture from Step 3 (10.5 g) and NBU4OAC (17g) dissolved in 250 ml acetic anhydride were heated to 110-120 °C 14 hours then cooled to ambient temperature. Excess acetic anhydride was removed under reduced vacuum. The residue was dissolved in 500 ml CH2CI2, washed twice with 200 ml apiece aqueous NaHCOj and brine, and dried. The solution was concentrated, the mixture purified by chromatography using silica gel and hexane/EtOAc, 8 1, and the product isolated in 60% yield as a cis/trans isomer mixture. 

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