A regiocontrolled synthesis of N7- and N9-guanine nucleosides

Abstract

The reaction of 2-0-acetylated and 2-0-benzoylated glycosides 3a,b/4a,b with silylated p-acetylguanine 7 selectively gave "'-guanine nucleosides 8a,b/Sa,b under kinetically controlled conditions (SnC14/CH3CN, room temperature), whereas 2-0-benzoylated glycosides 3b/4b selectively gave the isomeric Ns-guanine nucleosides lob/ 1 lb under thermodynamically controlled conditions (TMSOTf/(CH,Cl),, reflux). Unambiguous assignment of nucleoside structure was accomplished after hydrolysis (NH3/MeOH) of the initial products to the known nucleosides &, SC, lOc, and l l c followed by 'H and 13C NMR spectral analysis. The described procedures provide the best method to date for the selective synthesis of either N'or NB-guanine nucleosides from a common substrate. As part of a program directed toward the synthesis of the nucleoside antibiotics amipurimycin (1) and miharamycin (2),l we required a method for the synthesis ofNg-pyranosyl-2-aminopurines from their corresponding glycosidic precursors. In this context a coupling procedure that involved the use of a readily available silylated guanine derivative in conjunction with a Lewis acid catalyst seemed most appropriate even though the regioselectivity of this reaction (ie. Wvs Ng-glycosylation) is not generally high with this base.24 Once the desired Ng-nucleoside is (1) Amipurimycin: Goto, T.; Toya, Y.; Ohgi, T.; Kondo, T. Tetrahedron Lett. 1982, 1271. Miharamycin: Seto, H.; Koyama, M.; Ogino, H.; Teuruoka, T.; Inouye, S.; Otake, N. Ibid. 1983, 1805. ( 2 ) For a review of developments in the area of nucleoside synthesis, see.: Dekker, C. A.; Goodman, L. In The Carbohydrates, 2nd Ed.; Pipman, W., Horton, D., Herp, A., Eds.; Academic: New York, 1970. And more recently: Vorbrtiggen, H. NATO Adv. Study Zmt. Ser., Ser. A 1979,26, 35. 0022-3263/88/1953-1294$01.50/0 obtained, however, plodification of the8 guanine moiety to give the 2-aminopurine could then follow well, established procedure^.^ Herein we report on work which has cul-(3) (a) Lichtenthaler, F. W.; Voss, P.; Heerd, A. Tetrahedron Lett. 1974,2141. (b) Vorbniggen, H.; Krolikiewicz, K.; Bennua, B. Chem. Ber. 1981,114,1234. (c) Morr, M. Liebigs Ann. Chem. 1982,666. The NMR data reported in this paper seems to indicate that a (2.5:l) mixture of Ng:W regioisomers waa obtained rather than the reported anomeric mixture of Ng-nucleosides-see Table I. (d) For a related "transnucleosidation", see: Azuma, T.; Isono, K. Chem. Pharm. Bull. 1977,25, 3347. (4) Previous approaches to nucleosides (and nucleotides) that also employed guanine derivatives directly for the coupling include: (a) Imai, K.; Nohara, A.; Honjo, M. Chem. Pharm. Bull. 1966,14, 1377. (b) Nomura, H.; Suhara, I.; Uno, N. Ibid, 1967, 15, 1258. (c) Furukawa, Y.; Honjo, M. Zbid. 1968, 16, 1076. (d) Furukawa, Y.; Imai, K.; Honjo, M. Tetrahedron Lett. 1968,4655. (e) Suzaki, S.; Yamazaki, A.; Kamimura, A.; Mitaugi, K.; Kumashiro, 1. Chem.

Synthesis of Novel Thiopurine Pyranonucleosides: Evaluation of Their Bioactivity

“…It is generally accepted that N-9 nucleosides are thermodynamically favored over their N-7 isomers. Starting from the same substrate, regioselective synthesis of both N-7 and N-9 pyranosylguanine nucleosides has been achieved by application of kinetic and thermodynamic control reaction conditions respectively [36,37] In the present study, the structural differentiation of the purine base affects probably the stability of the intermediate transition state resulting in the case of thio purines more easily the thermodynamically favored N-9 isomers. …”

The effect of the glycosylation position on the base pairing and supramolecular structure of the 5′-deoxyribosyl Janus-type AT nucleosides

“…Just as for canonical nucleosides synthesis, when silylated base moieties contain more than one ring nitrogen atom, each of these nitrogen atoms can be possibly attached with the sugar residue, and the final products formation is either kinetically or thermodynamically controlled. For instance, the regio-controlled synthesis of N7 and N9 purine nucleoside derivatives have been investigated extensively [18]. Here, the existing of four nitrogen atoms on the pyrimido [4,5-d] pyrimidine ring also raises the same regio-selective problem.…”

Atom Transfer Radical Polymerization of Adenine, Thymine, Cytosine, and Guanine Nucleobase Monomers

“…27,28 In order to obtain the desired guanine monomer, we therefore adapted a procedure described by Benner et al 29 for selective N9 alkylation of guanine using Mitsunobu-type conditions, as depicted in Scheme 2. For selective N9 alkylation, an O6 and N2 protected guanine precursor was needed.…”