Synthesis and Biological Activity of Certain Derivatives of Oxazinomycin and Related Oxadiazole Nucleosides

Article abstract of DOI:10.1021/jm00142a010

Oxazinomycin was converted into 2',3',5'-tri-O-acetyloxazinomycin (2) and 2',3'-O-isopropyllideneoxazinomycin (3), respectively.Compound 3 was iodinated and reduced to provide 5'-deoxy-2',3'-O-isopropylideneoxazinomycin (5) which, after acid hydrolysis, provided 5'-deoxyoxazinomycin (6).Alternatively, the iodination of oxazinomycin followed by catalytic hydrogenation also provided 6.Oxazinomycin was treated with 2-acetoxybenzoyl chloride to provide 3'-O-acetyl-2'-chloro-2'-deoxyoxazinomycin (8) which, after reduction with tributyltin hydride, provided 3'-O-acetyl-2'-deoxyoxazinomycin (9).Oxazinomycin was also converted into oxazinomycin 5'-phosphate (10) and into O⁴,2'-anhydrooxazinomycin (11). 1,2,4-Oxadiazole-3,5-dione (12) was glycosylated to provide 2-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1,2,4-oxadiazole-3,5-dione (13) which, after deacetylation, provided 2-β-D-ribofuranosyl-1,2,4-oxadiazole-3,5-dione (14).Similarly, 12 provided 2-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-3,5-dione (17); 14 was also converted into the corresponding 2',3'-O-isopropylidene derivative 15.Compound 14 showed significant antiviral activity against herpes simplex virus type 1, in vitro.