Scheme 2.
Synthesis of the fully assembled ASOs. Shown are the chemical steps to synthesize a dinucleotide with thiophosphate linkage via solid-phase technique. The cycle is repeated to incorporate the remaining canonical bases as well as 7 and 8. Ammonia-mediated global deprotection and cleavage led to unprotected 11a-d which were subsequently reacted with 2 to furnish the final compounds 1a-d.
