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

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Title: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
Creators:
Lönnberg, Tuomas
Králíková, Šárka
Rosenberg, Ivan
Lönnberg, Harri
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 71, 6, pp. 859-870
Uncontrolled Keywords:Mechanisms, Kinetics, Hydrolysis, Nucleotides, Dinucleoside phosphonates, Nucleosides, RNA, Isomerizations, Phosphonate migration

Abstract

Isomerization of internucleosidic 3'-O-P-CH<sub>2</sub>-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 ((<i>R</i>,<i>S</i>)-<strong>1</strong>, (<i>R</i>,<i>S</i>)-<strong>2</strong>) or 5'-deoxyadenosine (<strong>3</strong>, <strong>4</strong>) bonded to the phosphorus atom through the C5'-atom. For comparative purposes, the hydrolytic stability of C5'-hydroxyphosphonate analogs derived from 2'-deoxyadenosine ((<i>R</i>,<i>S</i>)-<strong>5</strong>) has also been studied. In addition to the expected acid-catalyzed (pH &lt; 3) and pH-independent reactions (pH 3-9), the diastereomeric C5'-hydroxyphosphonate analogs ((<i>R</i>,<i>S</i>)-<strong>1</strong>, (<i>R</i>,<i>S</i>)-<strong>2</strong>), but not their deoxy counterparts (<strong>3</strong>, <strong>4</strong>), 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. <p>

Title: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
Creators:
Lönnberg, Tuomas
Králíková, Šárka
Rosenberg, Ivan
Lönnberg, Harri
Uncontrolled Keywords:Mechanisms, Kinetics, Hydrolysis, Nucleotides, Dinucleoside phosphonates, Nucleosides, RNA, Isomerizations, Phosphonate migration
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:71
Number:6
Page Range:pp. 859-870
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20060859UNSPECIFIED
ID Code:2512
Item Type:Article
Deposited On:06 Feb 2009 17:19
Last Modified:06 Feb 2009 16:19

Citation

Lönnberg, Tuomas; Králíková, Šárka; Rosenberg, Ivan; Lönnberg, Harri (2006) 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. Collection of Czechoslovak Chemical Communications, 71 (6). pp. 859-870. ISSN 0010-0765

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