Synthesis of new pseudonucleosides containing chiral cyclosulfamides as agycone

Article abstract of DOI:10.1081/NCN-120022608

A series of chiral cyclosufamides have been synthesized in four steps, starting from N-benzoylaminoacids. Regioselective glycosylation of these pseudopyrimidic heterocycles was carried out after deprotection. Best glycosylation results were obtained by pr

Full text of DOI:10.1081/NCN-120022608

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Synthesis of New Pseudonucleosides Containing Chiral
Cyclosulfamides as Agycone
Malika Berredjem a & Nour-Eddine Aouf a b
a Laboratoire de Chimie Bioorganique , Université Badji-Mokhtar , BP12 Annaba, Algeria
b Laboratoire de Chimie Bioorganique , Université Badji Mokhtar , BP12 Annaba, Algeria
Published online: 31 Aug 2006.
To cite this article: Malika Berredjem & Nour-Eddine Aouf (2003) Synthesis of New Pseudonucleosides Containing Chiral
Cyclosulfamides as Agycone, Nucleosides, Nucleotides and Nucleic Acids, 22:5-8, 671-673, DOI: 10.1081/NCN-120022608
To link to this article: http://dx.doi.org/10.1081/NCN-120022608
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 671–673, 2003
Synthesis of New Pseudonucleosides Containing Chiral
Cyclosulfamides as Agycone
*
Malika Berredjem and Nour-Eddine Aouf
´
Laboratoire de Chimie Bioorganique, Universite Badji-Mokhtar,
BP12 Annaba, Algeria
ABSTRACT
A series of chiral cyclosufamides have been synthesized in four steps, starting
from N-benzoylaminoacids. Regioselective glycosylation of these pseudopyri-
midic heterocycles was carried out after deprotection. Best glycosylation results
were obtained by preliminary silylation of cyclosulfamides, and their condensation
with a tetraacetylribofuranose and pentaacetylglucopyranose is described, which
yielded the pseudonucleosides in a b-anomeric configuration.
Key Words: Chlorosulfonyle isocyanate; Aminoacids; Cyclosulfamide; Glyco-
sylation; Regiospecific; Pseudonucleoside.
INTRODUCTION
Nucleosides and analogues such as pseudonucleosides have attracted a wide
interest in view of the importance of their biological activities. Many of them, nat-
ural or synthetic, are well known for their potent antiviral and antitumor activities.
The modification of the heterocyclic aglycone is important for the synthesis of new
nucleosidic analogues with potential antiviral and=or antitumoral activity.[1] In order
´
*Correspondence: Nour-Eddine Aouf , Laboratoire de Chimie Bioorganique, Universite Badji
Mokhtar, BP12 Annaba, Algeria; Fax: +213 38 872 789; E-mail: neaouf@yahoo.fr.
671
DOI: 10.1081/NCN-120022608
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

672
Berredjem and Aouf
to interfere with biological processes, it must be able to inhibit nucleoside biogenesis
enzymes, or to selectivily hybridise with natural nucleotides. In our previous
works, we reported the synthesis of new pseudonucleosides containing chiral sulfa-
hydanto¨ıns.[2,3]
Recently, we have reported the synthesis of new chiral 1,2,5 thiadiazolidines
1,1-dioxides and their natural amino acids derivatives.[4–5]
We describe here the synthesis of a series of pseudonucleosides containing chiral
cyclosulfamides as aglycone.
SYNTHESIS
The new Chiral cyclosulfamides[5] 1a–1b (sulfa-analogues of cyclic ureas) have
been synthesized starting from N-benzoylaminoacids (Val, Leu) and chlorosulfonyl
isocyanate (CSI), for these compounds the N[5] position was protected with a benzyl
group, removable by hydrogenolysis. Orthogonal protecting groups can be indepen-
dently removed in appropriate conditions (40% trifluoroacetic in dichloromethane
for the BOC group; Pd-C and ammonium formate for the benzyl group).
The regiospecific glycosylation of these pseudopyrimidic heterocycles was car-
ried out after silylation. The Vorbruggen method[5] of glycosylation was applied.
¨
This route requires preliminary silylation of the aglycone by BSA or HMDS. The
heterocycles 2a–2b, 3a–3b were first treated by hexamethyldisilasane (HMDS) or
bis-trimethylsilylacetamide (BSA) containing catalytic quantities of ammonium
sulphate.
The condensation with 1,2,3,4,6-penta-O-acetyl-b-D-glucopyranosyl and
1,2,3,5-tetra-O-acetyl-b-D-ribofuranose was carried out in acetonitril, in presence
of tin tetrachloride. Finaly the ester groups were removed by treatment with metha-
nolic-ammonia affording the corresponding pseudonucleosides.
þ
Scheme 1. (i): TFA, CH2Cl2 0ꢀC; (ii): NH4 HCOOꢁ (iii): HMDS, (NH4)2 SO4, SnCl4,
AcCN, 1,2,3,5-tetra-O-acetyl-b-D-ribofuranose=1,2,3,4,6-penta-O-acetyl-b-D-glucopyranosyl;
(iv): MeOH=NH3.

Synthesis of New Pseudonucleosides
673
The structure of the products was confirmed by usual spectroscopic
methods: IR, H and 13C, NMR, mass spectrometry and elemental analysis. The b
1
anomeric configuration of the pseudonucleosides was confirmed by NMR studies
(J10 ꢁ J20 ¼ 7.8 Hz).
CONCLUSION
We describe here the preparation of new pseudonucleosides containing chiral
cyclosulfamides. The structure of all the compounds were unambiguously confirmed
by spectroscopic methods. The biological evaluation of the resulting compounds and
their incorporation in biomolecules are currently in progress.
ACKNOWLEDGMENTS
This work is partially supported by: Algerian Ministry of Scientific Research,
National Agency for the Development Research in Health (ANDRS), Applied
Organic Chemistry Laboratory (FNR. 2000), and national fund of research.
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