Purine nucleosides. XVIII. Direct utilization of unsaturated sugars in nucleoside syntheses. Conformation and structure of cartain 9-(2-deoxy-D-erythro-pentopyranosyl)purines prepared from D-arabinal

Abstract

The direct acid-catalyzed fusion of 6-chloropurine (I) or 2,6-dichloropurine (II) with 3,4-di-O-acetyl-D-arabinal provided a 40-50 % crude yield of crystalline acetylated nucleoside derivatives. The major products were shown to be the corresponding 6-chloroor 2,6-dichloro-9-(3 ',4 '-di-O-acetyl--and ß-2 '-deoxy-o-ribopyranosyl)purine which were separated into pure anomers by preparative layer chromatography and fractional crystallization. The structures of the products were verified by an independent synthesis from the acid-catalyzed fusion of 1,3,4-tri-0-acetyl-2-deoxy-/3-o-ribopyranose and the appropriate purine, which yielded a similar anomeric mixture of the corresponding 9-(3 ',4 '-di-O-acetyl-2 '-deoxyribopyranosyljpurine in about 30% yield, presumably via a common intermediate carbonium ion at Q. The conformation and anomeric configuration has been assigned with the assistance of proton magnetic resonance studies utilizing the double-resonance or proton-proton spin decoupling technique. The ready availability of these 2 '-deoxynucleosides from D-arabinal provides extremely useful synthetic intermediate nucleosides for the preparation of many interesting 9-(2'-deoxy-D-ribopyranosyl)purines of known anomeric assignment. A number of these derivatives obtained by functional group replacement on the purine moiety are reported.The possibility of employing a glycal derivative directly in nucleoside synthesis was first suggested by Robins, et al.f in a model study utilizing various purines and 2,3-dihydropyran and 2,3-dihydrofuran.6•6The fusion procedure of nucleoside synthesis7-10 has proved very successful in recent years in our own laboratory and suggested the possibility of employing an appropriately acetylated glycal directly in an attempt to prepare 2 '-deoxyribopyranosylpurines by a fusion procedure. The use of a 1,2-unsaturated sugar derivative directly has several distinct advantages. For instance, previous procedures have utilized glycals as starting material for subsequent conversion to the requisite 2-deoxy-o-pyranosyl halides which have then been employed in the condensation with the mercury salt of a purine11•12 *or pyrimidine base.1314

Identification of the α and β Anomers of 1-(2-Deoxy-d-Erythro-Pentofuranosyl)-Oxaluric Acid at the Site of Riboflavin-mediated Photooxidation of Guanine in 2′-Deoxyguanosine and Thymidylyl-(3′-5′)-2′-Deoxyguanosine†

“…The sum of the H1′ couplings of α‐dOx is 8.7 Hz, almost 5 Hz smaller than the value for β‐dOx and dG due to a J(1′2′) of 1.8 Hz. The latter features are characteristic of the α and β furanosyl forms of pyrimidine (42–45), purine (46–49), urea (50) and imidazolone (51) 2′‐deoxyribonucleosides.…”

“…Relative to Tpβ‐dOx, the terminal ΣH1′ coupling constants of Tpα‐dOx is 5 Hz smaller and 3 J(1′2′) is only 2.0 Hz. The latter features are characteristic differences between the α and β furanosyl forms of pyrimidine and purine 2′‐deoxyribonucleosides (42–51).…”

Synthetic routes to 2′,3′-cyclopropanated and 2′,3′-unsaturated nucleosides

“…This approach to the synthesis of 2',3'-unsaturated nucleosides from a 2,3-unsaturated hexopyranoside via the corresponding acetate, offers at least one advantage over the existing and most commonly used 'glycal approach' (8, 9, 14-16). The method provides exclusively the 2',3'-unsaturated nucleosides, whereas the 'glycal approach' furnishes the 1',2'-unsaturated 3'-nucleosides (17,18) and/or 2'-deoxy nucleosides (8,(19)(20)(21) as side products, thereby increasing the difficulty in isolating the desired product. Further experiments to test the generality of the method are underway and will be reported in due course.…”

Ring Opening Photoreactions of 5‐bromouracil and 5‐bromo‐2′‐deoxyuridine With Selected Alkylamines

“…Proton NMR spectral dara for the furanosyl and pyranosyl deoxyribonucleosides of thymine A number of references can be found in the literature concerning the preparation and structural analysis of the a and f3-furanosyl and a-and P-pyranosyl forms of pyrimidine (Lemieux, 1961; Cleve et al, 1973; Remin et al, 1975;Cadet er al., 1980) and purine (Robins and Robins, 1%5; Leutzinger et al, 1968;Mariaggi er al., 1979;Berger and Cadet, 1985) 2'-deoxyribonucleosides. In the work described in these references, 'H-NMR was shown to be an invaluable tool for structural and conformational assignments of such products.…”

“…For comparison purposes, the results obtained for the two BrdU-ethylamine products (IIIa and IIIb) are presented in Table Al. Detailed analyses of the NMR data, with regard to assignment of each sugar structure and conformation, have already been made (Lemieux, 1%1;Remin et al, 1975;Robins and Robins, 1965;Mariaggi et al, 1979;Leutzinger et al, 1968;Cadet et al, 1980) and these will not be repeated here. It is worth mentioning that the data reported here for the furanosyl forms are in good agreement with the data reported by Lemiew (1961) and Cadet et al (1980).…”