Collect. Czech. Chem. Commun. 2006, 71, 859-870

Kinetics and Mechanisms for the Isomerization of Internucleosidic 3'-O-P-CH2-5' and 3'-O-P-CH(OH)-5' Linkages to Their 2',5'-Counterparts

Tuomas Lönnberga, Šárka Králíkováb, Ivan Rosenbergb and Harri Lönnberga,*

a Department of Chemistry, University of Turku, 20014 Turku, Finland
b Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, CZ-166 10 Prague 6, Czech Republic


Isomerization of internucleosidic 3'-O-P-CH2-5' and 3'-O-P-CH(OH)-5' phosphonate linkages to their 2',5'-counterparts has been studied over a wide pH-range. The model compounds employed are phosphonate analogs of adenylyl-(3',5')-adenosine and adenylyl-(2',5')-adenosine having either adenosine ((R,S)-1, (R,S)-2) or 5'-deoxyadenosine (3, 4) bonded to the phosphorus atom through the C5'-atom. For comparative purposes, the hydrolytic stability of C5'-hydroxyphosphonate analogs derived from 2'-deoxyadenosine ((R,S)-5) has also been studied. In addition to the expected acid-catalyzed (pH < 3) and pH-independent reactions (pH 3-9), the diastereomeric C5'-hydroxyphosphonate analogs ((R,S)-1, (R,S)-2), but not their deoxy counterparts (3, 4), have been observed to undergo a hydroxide-ion-catalyzed isomerization around pH 11 (90 °C). Evidently a hydrogen bond between the dianionic phosphorane and the C5'-hydroxy group stabilize the phosphorane to such an extent that isomerization via kinetically invisible protonation to monoanion becomes possible. The mechanisms of the isomerization reactions taking place under various conditions are discussed.

Keywords: Nucleosides; Nucleotides; RNA; Dinucleoside phosphonates; Phosphonate migration; Kinetics; Mechanisms; Hydrolysis; Isomerizations.

References: 34 live references.