合成路线1

Acylation of inosine (I) with Ac2O in the presence of pyridine yields inosine triacetate (II), which is then protected as the N-MEM derivative (III) using chloromethyl methyl ether and DIEA in CH2Cl2. Deacetylation of compound (III) with NH3 in MeOH affords 1-MEMinosine (IV), which finally undergoes purine ring opening in refluxing NaOH .
In a related method, acadesine is obtained by MEM protection of inosine acetate (II) with chloromethyl methyl ether by means of NaH in dioxane, and subsequent purine ring hydrolysis with NaOH in refluxing EtOH .
Similarly, direct hydrolysis of unprotected inosine (I) with KOH in water at 130 °C produces a mixture of acadesine and 9-β-D-ribopyranosylhypoxanthine, from which acadesine can be isolated using column chromatography .
An alternative strategy is the hydrolysis of the imidazolecarbonitrile (V) with NaOH at 100 °C .
In a different approach, reaction of 2’,3’-O-isopropylideneinosine (VI) with 2,4-dinitrochlorobenzene (DNCB) by means of K2CO3 at 80 °C yields N1-(2,4-dinitrophenyl)-2’,3’-O-isopropylideneinosine (VII), which is then O-deprotected with HCOOH in H2O to give 1-(2,4-dinitrophenyl) inosine (VIII). Regioselective attachment of the triol (VIII) to MMTCl resin in the presence of DMAP in pyridine provides the resin-bound compound (IX), which is then submitted to purine ring hydrolysis with EDA in DMF, and subsequent deprotection of the obtained intermediate with TFA in CH2Cl2 .