Naphthaloyl group: a new selective amino protecting group for deoxynucleosides in oligonucleotide synthesis

Abstract

ARCHANA DIKSHIT, MANJULA CHADDHA, R. K. SINGH, and KRISHNA MISRA. Can. J . Chem. 66, 2989 (1988). The naphthaloyl group has been found to be a selective amino protecting group for deoxycytidine, deoxyadenosine, and deoxyguanosine in oligodeoxyribonucleotide synthesis. All three protected monomers obtained (78-85%), being six-membered cyclic imides, were fairly stable. These protected monomers were used successfully for the preparation of dimers (phosphodiester approach) and tetramers (phosphotriester approach) in solution as well as solid phase, respectively. The group acted as a purification tool due to its high lipophilicity. No adverse effect has been observed either on the glycosidic bond (depurination) or the intemucleotidic bond during its removal. The monomeric units were characterized by UV, NMR, and elemental analyses whereas the tetramers were characterized by enzymatic hydrolyses with snake venom phosphodiesterase followed by alkaline phosphatase.ARCHANA DIKSHIT, MANJULA CHADDHA, R. K. SINGH, et KRISHNA MISRA. Can. J . Chem. 66, 2989 (1988). On a trouvC que le groupe naphtaloyle constitue un groupe protecteur selectif de la fonction amine de la dCoxycytidine, de la dCoxyadCnosine et de la dkoxyguanosine dans la synthkse de 1'oligodCoxyribonuclCotide. Les trois monomkres protCgCs obtenus (78-85%) sont des imides cycliques i six chainons assez stables. On a~u t i l i s~ avantageusement ces trois monomkres protCgCs dans la prkparation des dimkres (approche phosphodiester) et des titramkres (approche phosphotriesters) en solution aussi bien qu'en phase solide respectivement. La grande IipophilicitC de ce groupe en fait un outil de purification. On n'a pas observC d'effets contraires ni sur la liaison glycosidique (dipurination) ni sur la liaison intemucliotidique lors de la diprotection. On a caractCrisC les unitis monornkres par ultraviolet, par risonance magnitique nuclCaire et par analyse ClCmentaire tandis que l'hydrolyse enzymatique par le phosphodiestirase du venin de serpent suivie d'une phosphatase alcaline ont permis de caractiriser les titramkres.[Traduit par la revue] Introduction The importance of synthetic oligodeoxyribonucleotides in molecular biology (1)(2)(3)(4)(5) has long attracted attention to the

Synthesis and Biophysical Properties of Oligodeoxynucleotides Containing 2′‐Deoxy‐5‐(4‐nitro‐1H‐imidazol‐1‐yl)‐β‐D‐uridine and 2′‐Deoxy‐5‐(1,3‐dioxo‐1H‐benzo[de]isoquinolin‐2(3H)‐yl)‐β‐D‐uridine Monomers

“…NH 3 (508 for 4 h) [12]. Our results showed that the 1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl moiety formed on 5-aminouracil is relatively stable and can be successfully installed on ODN derivatives when using mild deprotection conditions.…”

“…This reaction was performed in a mixture of EtOH and DMSO in the presence of Et 3 N and DMAP. The use of the typical solvents for such a transformation like glacial AcOH [11] or pyridine [12] were not efficient because of poor solubility of 1 in these solvents.…”