Oligodeoxyribonucleotides Synthesis: Phosphoramidite Approach

The development of deoxyribonucleoside phosphoramidite derivatives for the synthesis of oligodeoxyribonucleotides was first described by Beaucage and Caruthers ( 1 ) in 1981. The conceptual basis of this methodology emerged as a modification of the “phosphorodichloridite” coupling procedure reported earlier by Letsinger and coworkers ( 2 ). Essentially, the approach involved the reaction of the protected deoxyribonucleosides 1a–d (Fig. 1 ) with chloro-( N,N -dimethylamino) methoxyphosphine ( 2 ) in the presence of N,N -diisopropylethylamine. The rapid reaction yielded the deoxyribonucleoside phosphoramidites 3a–d (Fig. 1 ), which were isolated by precipitation and stored as dry powders.   Fig. 1.