A Novel General Methodology for Oligodeoxyribonucleotide Synthesis, Using a Modification of the H-Phosphonate Procedure

Oxiranes are famous and very interesting compounds with a wide range application, they have found in the chemistry and industry. It is well known, that their ring opening is possible as in acidand in base reaction conditions, as well as by nucleophilic attack from the internal or external nucleophile molecule. The acid-catalyzed ring opening reaction has been described by T. Biela, P. Kubisa, R. Szymanski and S. Penczek [1, 2]. When this reaction is carried out with H-phosphonic acid (phosphorous acid), it leads to the formation of 2-hydroxyalkyl H-phosphonate (beta-hydroxyalkyl phosphite), and then – to the formation of 2-hydroxyalkyl H-phosphonate diester (due to the anchymeric assistance by the vicinal hydroxyl group, facilitating the faster reaction of 2-hydroxyalkyl H-phosphonate with the second oxirane molecule), which is the actual reactive intermediate, causes the phosphonylation. The participation of the ester 2-OH group of 2-hydroxyalkyl Hphosphonate diester (by an intramolecular hydrogen bonding) in hydrolysis or alcoholysis (nucleophilysis) reaction, which is accompanied by the 1,2-diol leaving as a model reaction of the electrophilic catalysis by the vicinal β-hydroxyl group in aprotic organic media is used by the large ribozymes (group I, group II, ribonuclease P and spliceosomal introns) [3]. The other reaction, which is accompanied by the assistance of beta-hydroxyl group in the bis-(2-hydroxyalkyl) H-phosphonate as nucleophilic catalyst in aqueous conditions, is the reaction, characterized for the ribonuclease A catalyzed hydrolysis [4] and leads to phosphate migration or mono-ol exchange [5-7]. The bis-(2-hydroxyalkyl) H-phosphonate actually is the reactive intermediate, participating in a variety of reactions, susceptible for attack by different nucleophiles and leading to different types of products. When this reactive intermediate is attacked by the alcohol molecules (methanol, ethanol, propanol, isopropanol, sugar or the ribose/2’deoxyribose ring from the nucleoside), the process is characterized as a typical transesterification reaction.