Abstract
1,2,4-Triazole nucleoside analogues bonded at N-1 of the base were synthesized by addition of N -halo-3,5-dibromo-1,2,4-triazoles to 1,2-unsaturated carbohydrate derivatives (glycals). Examples are given for 1,5-anhydro-3,4,6-tri-O -acetyl-2-deoxy-d -arabino -hex-1-enitol (tri-O -acetyl-d -glucal), and 1,5-anhydro-3,4,6-tri-O -benzyl-2-deoxy-d -arabino -hex-1-enitol (tri-O -benzyl-d -glucal), respectively. The graduated reactivity of the three halogens [C-5 (triazole) > C-2 (sugar) > C-3 (triazole)] in the addition products allows subsequent regioselective replacement and deprotection reactions like hydrodehalogenations, nucleophilic substitutions (by methoxide, hydrazine, benzylamine, thiophenolate), deacetylations, and debenzylations, respectively. Thus, the paper opens a new synthetic approach to triazole nucleoside analogues of 2-deoxy-sugars. X-ray analyses support the structures of nine products.
Key words
nucleoside analogues - 1,2,4-triazoles - additions to d -glucals - nucleophilic substitutions - hydrodehalogenations
References
1 Kröger C.-F.
Miethchen R.
Chem. Ber.
1967,
100:
2250
2 Becker HGO.
Eisenschmidt V.
Bubig M.
Jähnisch K.
Klein N.
Kowalski W.
Misselwitz R.
Müller R.
Reimann P.
Roth C.
Sauter W.-D.
Schößler W.
Thorein B.
Z. Chem.
1969,
9:
325
3 Unlike 3,5-dibromo-1,2,4-triazole itself, which is deprotonated and so deactivated by sodium hydroxide, the corresponding N -alkyl derivative reacts with this reagent via 3-bromo-5-hydroxy-1-methyl-1,2,4-triazole to the tautomeric 3-bromo-1-methyl-1,2,4-triazolone-(5). The reaction stops at this stage, because the 3-bromo-1-methyl-1,2,4-triazolone-(5) is now likewise deactivated by deprotonation: Miethchen, R.; Kröger, C.-F. unpublished results.
4 Becker HGO, Eisenschmidt V, and Wehner K. inventors; Ger. Pat. DD 19670415. The data reported for nucleophilic substitutions on 3,5-dibromo-1,2,4-triazole with alkali hydroxides and alkoxides in following patent are not correct:
; Chem. Abstr. 1969 , 70 , 28922
5 Zumbrunn A.
Synthesis
1998,
1357
6 Wu Q.
Qu F.
Wan J.
Zhu X.
Xia Y.
Peng L.
Helv. Chim. Acta
2004,
87:
811
7 Kovalew EG.
Postowskii IJa.
Khim. Geterotsikl. Soedin.
1968,
740
8 Dallacker F.
Minn K.
Chem.-Ztg.
1986,
110:
101
9 Bowles WA.
Robins RK.
J. Am. Chem. Soc.
1964,
86:
1252
10 De las Heras FG.
Stud M.
Tetrahedron
1977,
33:
1513
11 Herscovici J.
Montserret R.
Antonakis K.
Carbohydr. Res.
1988,
176:
219
12 Winterfeld GA.
Das J.
Schmidt RR.
Eur. J. Org. Chem.
2000,
3047
13 Herdewijn P.
Antisense Nucleic Acid Drug Dev.
2000,
10:
297
14 Herdewijn P. In
Recent Advances in Nucleosides
Chu CK.
Elsevier;
Amsterdam:
2002.
p.239
15 Eschenmoser A.
Loewenthal E.
Chem. Soc. Rev.
1992,
21:
1
16 Witkowski JT.
Robins RK.
Chemistry and Biology of Nucleosides and Nucleotides
Academic Press;
New York:
1979. ; and references therein
17 Kane JM.
Dudley MW.
Sorenson SM.
Miller FP.
J. Med. Chem.
1988,
31:
1253
18 Hanna NB.
Dimitrijevich SD.
Larson SB.
Robins RK.
Revankar GR.
J. Heterocycl. Chem.
1988,
25:
1857
19 Michael J.
Larson SB.
Vaghefi MM.
Robins K.
J. Heterocycl. Chem.
1990,
27:
1063 ; and references therein
20 Thiem J.
Klaffke W.
Top. Curr. Chem.
1990,
154:
285 ; and references therein
21 Collins P.
Ferrier R.
Monosaccharides, their Chemistry and their Roles in Natural Products
J. Wiley & Sons;
Chichester:
1995.
22 Lafont D.
Boullanger P.
Rosenzweig M.
J. Carbohydr. Chem.
1998,
17:
1377
23 The use of solvents like CHCl3 and NMP gave only low yields of the desired compounds. THF proved to be unsuitable, because it was attacked by 1,3,5-tribromo-1,2,4-triazole (1 ) resulting in ring-opening and insertion of the 1-oxy-tetramethylene chain between the glycosidic position and N -1 of the triazole ring. The diastereomeric O -glyco-sides (54%) were formed along with about 26% of the desired products: Christiansen, A.; Miethchen, R. unpublished results.
24 Tribromo derivative 5 , EtMgCl/[Fe(acac)3 ] in THF/NMP gave 1-(3,4,6-tri-O- acetyl-2-deoxy-α-d -mannopyranosyl)-3-bromo-1H -1,2,4-triazole along with dibromo compound 13 .
25a Kudelska W.
Czyzewska-Chlebny J.
Michalska M.
Polish J. Chem.
1994,
68:
1767
25b Rauter AP.
Figueiredo J.
Ismael M.
Canda T.
Font J.
Figueredo M.
Tetrahedron: Asymmetry
2001,
12:
1131
26 Cremer D.
Pople JA.
J. Am. Chem. Soc.
1975,
97:
1354
27 Crystallographic data for the structures in this paper have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication nos. CCDC 265777 (11 ), 265778 (17 ), 276274 (5 ), 276275 (6 ), 276276 (7 ), 276277 (8 ), 276278 (13 ), 276279 (14 ), and 276280 (30 ). Copies of these data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk or via www.ccdc.cam.ac.uk/conts/retrieving.html.
