SYNTHESIS OF CARBON-3-SUBSTITUTED 1,5,9-TRIAZACYCLODODECANES, RNA CLEAVAGE AGENTS SUITABLE FOR OLIGONUCLEOTIDE TETHERING

Two derivatives of 1,5,9-triazacyclododecane bearing an alkylamino tet her group at carbon-3 (7 and 13) were synthesized. The first of them, 7, was prepared starting from diethyl 2-(2-cyanoethyl)malonate and the second one, 13, from glycerol. In both cases, the cyclization reactio n was performed by allowing the corresponding ditosylates (5 and 12) t o react with TBD. The guanidinium salts formed were reduced in situ to the orthoamides (6 and 12), acid-catalyzed hydrolysis of which yielde d the title compounds. The suitability of the azacrowns prepared for o ligonucleotide tethering is also demonstrated.