Synthesis and antiviral activity of stereoisomeric eritadenines

D-Eritadenine ( Ia ) and L-eritadenine ( IIa ) were prepared from 5-(adenin-9-yl)-5-deoxyaldofuranoses or enantiomeric 2,3-disubstituted erythronolactones ( VIIIb, c, XIV ). Oxidation of methyl 2,3-O-isopropylidene-D-ribofuranoside ( IX ) with periodate in the presence of ruthenium, followed by acid hydrolysis and reduction with sodium borohydride, afforded L-ribonolactone ( XI ). Its 2,3-O-isopropylidene derivative was subjected to alkaline hydrolysis, followed by oxidation with periodate, reduction with sodium borohydride and reaction with cyclohexanone to give 2,3-O-cyclohexylidene-L-erythronolactone ( XIV ). Condensation of [U- 14 C]-adenine with VIIIb , followed by acid hydrolysis, afforded [U- 14 C-adenine]-D-eritadenine. The threo -eritadenines III and IV were prepared by oxidation of 1-(adenin-9-yl)-1-deoxy-2,3-O-isopropylidenethreitols XVI and XVII with sodium periodate in the presence of ruthenium, followed by acid hydrolysis. Reaction of 9-(2,2-diethoxyethyl)adenine ( XIX ) with malonic acid gave 4-(adenin-9-yl)-3-butenoic acid ( XXI ); its methyl ester XXII , prepared by treatment with methanol, was isomerized with triethylamine to give methyl 4-(adenin-9-yl)-2-butenoate ( XXIII ). Hydroxylation of XXIII with osmium tetroxide afforded the racemic mixture of D- and L- threo -eritadenine ( III + IV ). Eritadenines Ia and IIa were active against vaccinia, measles and vesicular stomatitis virus. Eritadenine Ia was also effective against reo- and parainfluenza virus. In general, the antiviral activity of the eritadenines decreased in the order D- erythro ( Ia ) > L- erythro ( IIa ) > D- and L- threo ( III, IV ).