Design, Synthesis, and Antiviral Activity of Novel Ribonucleosides of 1,2,3-Triazolylbenzyl-aminophosphonates

Ouahrouch, Abdelaaziz; Taourirte, Moha; Schols, Dominique; Snoeck, Robert; Andrei, Graciela; Engels, Joachim W.; Lazrek, Hassan B.

The synthesis of the desired compounds (4a-j and 5a-j) is depicted in Scheme 1. Initially, the a-aminophosphonate compounds were prepared in good yields via the Kabachnik-Fields reaction. The 4-[(trimethylsilyl)ethynyl]benzaldehyde 1 was reacted with diethylphosphite and corresponding amine in acetonitrile using molecular iodine as catalyst [22] [23] [24] . The latter is low-priced, readily available, non-metallic, and nontoxic. The mixture was stirred at room temperature for 1 h to get compounds 2a-j. The next step is deprotection of the trimethylsilyl group. For this purpose, tetrabutylammonium fluoride (TBAF) in tetrahydrofurane (THF) was used to give the terminal alkyne [25] . The structures of 2e, 2f, 3d, and 3g were confirmed by X-ray diffraction (Fig. 1 ). According to the crystal data, the structures are similar for these compounds. The P-C bond has a staggered conformation, with the two six-membered groups with respect to the P --O double bond. The two benzene rings are almost perpendicular in all four compounds. In each crystal structure (2e, 3d, and 3g), the molecules are arranged as centrosymmetric or pseudocentrosymmetric dimers related by two N-HÁ Á ÁO --P hydrogen bonds. On the other hand, in the crystal structure of 2f, the hydrogen bond N-HÁ Á ÁO --P is not found, and the molecules are arranged as centrosymmetric dimers linked by C methyl -HÁ Á ÁO --P hydrogen bonds [26] .