Rearrangement reactions of guanosine cyclonucleosides and their analogs

Article abstract of DOI:10.1081/NCN-120022622

Under acid-catalyzed transglycosylation conditions 5′ ,8-cyclo-8-oxoguanine nucleosides undergo a ring-opening reaction to 8-oxoguanine derivatives, instead of the 7-9 isomerization.

Full text of DOI:10.1081/NCN-120022622

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Rearrangement Reactions of Guanosine
Cyclonucleosides and Their Analogs
Jerzy Boryski a b & Tomasz Zandecki a
a Institute of Bioorganic Chemistry, Polish Academy of Sciences , Poznan, Poland
b Institute of Bioorganic Chemistry, Polish Academy of Sciences , Noskowskiego 12/14,
PL-61704, Poznan, Poland
Published online: 31 Aug 2006.
To cite this article: Jerzy Boryski & Tomasz Zandecki (2003) Rearrangement Reactions of Guanosine Cyclonucleosides and
Their Analogs, Nucleosides, Nucleotides and Nucleic Acids, 22:5-8, 735-737, DOI: 10.1081/NCN-120022622
To link to this article: http://dx.doi.org/10.1081/NCN-120022622
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 735–737, 2003
Rearrangement Reactions of Guanosine Cyclonucleosides
and Their Analogs
*
Jerzy Boryski and Tomasz Zandecki
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
ABSTRACT
Under acid-catalyzed transglycosylation conditions 50,8-cyclo-8-oxoguanine
nucleosides undergo a ring-opening reaction to 8-oxoguanine derivatives, instead
of the 7–9 isomerization.
Key Words: Guanine cyclonucleosides; 8-Oxoguanine nucleosides; Transglyco-
sylation.
It has been shown that fully protected 6-oxopurine nucleosides (e.g., guanosine,
!
inosine) readily undergo a reversible 7 9 transglycosylation in the presence of acidic
catalysts, and only N7 and N9 of the imidazole ring may act as donors or acceptors
of a glycosyl cation.[1–3] The glycosyl migration process is an intermolecular reaction
and therefore, the 6-oxopurine nucleosides may serve as versatile substrates in the
synthesis of new nucleoside analogs by applying the exchange methods.[1,4–6] The
transglycosylation reactions have never been studied in the case of purine cyclo-
nucleosides, i.e., in situation, where the sugar portion and the purine part are linked
together with an additional chemical bond, besides the N-glycosylic one. In the
*Correspondence: Jerzy Boryski, Institute of Bioorganic Chemistry, Polish Academy of
Sciences, Noskowskiego 12=14, PL-61704 Poznan, Poland; Fax: +48 61 852 0532; E-mail:
jboryski@ibch.poznan.pl.
735
DOI: 10.1081/NCN-120022622
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

736
Boryski and Zandecki
Scheme 1. i, p-TsOH (1 eq. ), C6H5Cl, reflux, 2.5 h; ii, Et3N, CH3Cl, 48ꢀC, 22 h, or DBU,
DMF, 65ꢀC, 30 min; iii, 1,2,3,5-tetra-O-acetyl-b-D-ribofuranose or AcOCH2OCH2CH2OAc,
p-TsOH, C6H5Cl, reflux, 30 min.
present study, the model compounds (1a, b) of structure of 50,8-cyclo-8-oxonucleo-
sides were prepared from guanosine.
A preliminary study of transglycosylation reactions (refluxing in chlorobenzene
in the presence of p-toluenesulfonic acid) of 50,8-cyclo-8-oxo-20,30-O-isopropylidene-
N2-guanosine (1a)[7] gave quite unexpected results (Sch. 1). The cyclonucleoside did
!
not undergo the 7 9 isomerization, which could be anticipated by comparison with
‘regular’ 6-oxopurine nucleosides.[2] Instead of the N-glycosylic bond, the 50,8-oxy-
gen bridge was cleaved, resulting in the formation of 50-tosyl-8-oxoguanine deriva-
tive (2a; 77%). In addition, a dimer 3a was isolated from the reaction mixture as a
side-product (7%). In a similar manner, the pseudosugar analog 1b[8] was trans-
formed to compound 2b (66%). The reaction mechanism can be explained in the fol-
lowing way. After protonation of N7, a nucleophilic attack of tosyl anion at C50
results in the ring opening and the formation of 8-oxoguanine derivatives. The trans-
formation is reversible: treatment of 2a with bases (triethylamine, DBU) gave the

Reactions of Guanosine Cyclonucleosides
737
starting cyclonucleoside 1a. Recyclization of the pseudosugar analog 2b was consid-
erably slower.
In turn, reactions of 1 with 1,2,3,5-tetra-O-acetyl-b-D-ribofuranose or with 2-
acetoxyethyl acetoxymethyl ether (an acyclic analog of peracylated sugar) gave
7,9-diglycosyl-8-oxoguanine compounds of the type 4a. Interestingly, compound 1
did not undergo isomerization when subjected to action of sodium O,O-diethyl phos-
phate, an effective catalyst in the 1 ! 3 transglycosylation of O2,30-cycloanhydro-
thymidine.[9]
Structure of all obtained products were confirmed by 1H and 13C NMR spectro-
scopy, mass spectrometry and UV analysis.
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