Synthesis of complementary DNA fragments via phosphotriester intermediates

Abstract
The preparation of the complementary oligodeoxyribonucleotides Ia,b and II via a modified phosphotriester method is described. The synthesis of these compounds was accomplished by using: (a) the levulinyl group for temporary and persistent blocking of the 5′‐hydroxyl; (b) the monofunctional phosphorylating agent 2,2,2‐trichloroethyl 2‐chlorophenyl phosphorochloridate (3) to introduce the phosphate moiety at the 3′‐position; (c) the benzoyl group to protect the terminal 3′‐hydroxyl; (d) acyl groups for the protection of the exocyclic amino functions of the bases; and (e) 1‐(2,4,6‐triisopropylbenzenesulphonyl)‐3‐nitro‐1,2,4‐triazole (TPS‐NT, 11c) as activating agent in the formation of phosphotriester linkages. Final removal of all protecting groups was performed by fluoride ion treatment followed by aqueous ammonia. The oligonucleotides Ia,b and II were, after purification, isolated in good yields and, as followed from HPLC analysis, in high purity.

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