Controlling <i>para</i> -Quinone Methide Alkylation Impurities with Thiols during Phosphorodiamidate Morpholino Oligomer Synthesis

The use of doubly protected morpholino guanosine in the synthesis of PMO sequences generates a reactive para-quinone methide byproduct upon deprotection with concentrated ammonium hydroxide. Thiols are explored as potential scavengers to control the formation of PMO-alkylation impurities caused by para-quinone methide. The optimal concentration of thiol for effective control is determined.