Selective O-protection of compound (I) by treatment with tert-butyldiphenylsilyl chloride in pyridine affords derivative (II), which is selectively mesylated by means of methanesulfonyl chloride (MsCl) and Et3N in dichloromethane to provide protected derivative (III). Treatment of (III) with tert-butyldiphenylsilyl chloride and imidazole in DMF yields totally protected carbohydrate (IV), which is converted into the adenosine-like derivative (VI) by condensation with adenine (V) by means of K2CO3 and 18-crown-6 in DMF, followed by TBDPS removal by means of NH4F in MeOH. Treatment of (VI) with trimethyl silyl chloride in pyridine followed by reaction with benzoyl chloride (VII) and treatment with NH3/H2O gives benzoylated compound (VIII), which then reacts with 4,4'-dimethoxytrityl chloride and DIEA in pyridine to afford protected isodeoxyadenosine (IX). Derivatization of (IX) by reaction with o-Cl-Ph-O-P(O)(triaz)2 in THF provides mononucleotide (X), which is then condensed with deoxynucleoside (XI) by means of TPS and TAZ in pyridine to give dinucleotide (XII). Partial deprotection of (XII) by reaction with 2,2-dichloroacetic acid in dichloromethane furnishes compound (XIII). Finally, the target product is obtained by condensation of (XIII) with phosphoric acid derivative (XIV) by means of DCC in pyridine, followed by treatment with NH3/H2O.

The condensation of the cyclic sulfite (I) with N6-benzoyladenine (II) gives the isoadenosine (III), which is condensed with 2-chlorophenylphosphono-bis-triazolide (ClPTr) to yield the phosphate diester (IV). The condensation of (IV) with the deoxycytidine (V) by means of triisopropylbenzenesulfonyl tetrazolide (TPS-TAZ) affords the phosphoric ester (VI), which is treated with dichloroacetic acid (Cl2HOAc) in order to eliminate the dimethoxytrityl protecting group and provide the hydroxymethyl derivative (VII). The phosphorylation of (VII) by means of 2-cyanoethyl phosphate (VIII) gives the protected intermediate (IX), which is finally treated with hot NH4OH to yield the target bis nucleoside phosphate.

Selective O-protection of compound (I) by treatment with tert-butyldiphenylsilyl chloride in pyridine affords derivative (II), which is selectively mesylated by means of methanesulfonyl chloride (MsCl) and Et3N in dichloromethane to provide protected derivative (III). Treatment of (III) with tert-butyldiphenylsilyl chloride and imidazole in DMF yields totally protected carbohydrate (IV), which is converted into the adenosine-like derivative (VI) by condensation with adenine (V) by means of K2CO3 and 18-crown-6 in DMF, followed by TBDPS removal by means of NH4F in MeOH. Treatment of (VI) with trimethyl silyl chloride in pyridine followed by reaction with benzoyl chloride (VII) and treatment with NH3/H2O gives benzoylated compound (VIII), which then reacts with 4,4'-dimethoxytrityl chloride and DIEA in pyridine to afford protected isodeoxyadenosine (IX). Derivatization of (IX) by reaction with o-Cl-Ph-O-P(O)(triaz)2 in THF provides mononucleotide (X), which is then condensed with deoxynucleoside (XI) by means of TPS and TAZ in pyridine to give dinucleotide (XII). Partial deprotection of (XII) by reaction with 2,2-dichloroacetic acid in dichloromethane furnishes compound (XIII). Finally, the target product is obtained by condensation of (XIII) with phosphoric acid derivative (XIV) by means of DCC in pyridine, followed by treatment with NH3/H2O.