Compounds 2, 3 and 4 were obtained from key compound 20 via reductive amination of the aldehyde 21 that was prepared in three steps from l-aspartic acid following a published procedure [25]. Reductive amination was conducted in the presence of sodium triacetoxyborohydride and acetic acid [26]. The resulting fully protected dinucleoside 22 was isolated in high yield (93%). Then, sugar hydroxyls and amine were deprotected by TFA treatment and afforded methyl ester derivative 3. Subsequent basic treatment with LiOH converted the methyl ester in carboxylic acid and dinucleoside 2 with α-amino acid chain similar to that of SAM was obtained. Finally, the SAM analogue 4 with an amide function instead of a carboxylic acid in α-amino acid chain was prepared from 22 upon a final treatment with 7 M methanolic ammonia solution. Dinucleosides 5, 6 and 7 were rather synthesized through N-alkylation of 20 with 1-bromobutane, 1-bromo-3-phenylpropane or methyl-4-bromobutyrate, respectively, in N-methylmorpholine in the presence of diisopropylethylamine (DIEA) at 110 °C under microwave. These specific conditions were optimized for a successful synthesis of 23, 24 and 25 with an average 50% yield. This moderate yield results from double N-alkylations (observed in mass spectrometry) and incomplete reactions. Increasing temperature of the reactions neither did drive the reaction to completion. Next, 23, 24 and 25 were deprotected upon TFA treatment to obtain N-alkyl derivatives 5, 6 and 7, respectively. Subsequently, an additional basic treatment with 2 M LiOH was applied to 7 to convert the methyl ester moiety into the carboxylic acid-ended alkyl chain of compound 8. The same synthetic route used for the preparation of nosyl-containing dinucleoside 9 was followed to synthesize compounds 10–13 with diverse Ns-amide moieties as analogs of the nosyl group (Scheme 3). The reaction of 5′-amino-2′,3′-isopropylidene adenosine [23] with four diversely substituted (OMe, CF3, Cl) and commercially available nitrobenzenesulfonyl chloride reagents afforded the corresponding N-nosyl adenosines 26–29 with 40–72% yield [[27], [28], [29], [30]]. Their subsequent coupling with 17 in the presence of K2CO3 and KI gave the corresponding dinucleosides 30–33 in moderate yields from 43 to 52%. A final TFA treatment provided the respective N-nosyl adenine dinucleosides 10–13 which were purified by reversed-phase chromatography (Yield 13–20%).