A ¹H NMR Study of the Syn-Anti Dynamic Equilibrium in Adenine Nucleosides and Nucleotides with the Aid of Some Synthetic Model Analogues with Fixed Conformations

Abstract

The syn-anti equilibrium about the glycosidic bond in adenosine and some related analogues was studied by means of 1H NMR spectroscopy, with the aid of several model analogues fixed in given conformations either by intramolecular bonding, or by introduction of a bulky substituent. A model unambiguously and exclusively in the syn conformation is 8-(α-hydroxyisopropyl) adenosine; while one fixed in the a n ti conformation is 8,5′-anhydro-8-oxoadenosine. A new analogue, fixed in the high an ti conformation, is 8,2′-O-isopropylidenearabinofuranosyladenine. Several additional new model compounds were synthesized and their properties are described.With the aid of these models, the syn-anti dynamic equilibrium was examined for adenosine and some related compounds in different solvent systems, and the conformer populations evaluated quantitatively. The validity of the procedure applied, and the accuracy of the results, are critically examined, and compared with findings obtained by other procedures. Available literature data on the syn-anti equilibrium in other 8-substituted adenosines are re analyzed in the light of the present results. An analysis is also presented of the interdependence of the various conformational parameters, i. e. conformation about the glycosidic bond and those of the sugar ring and exocyclic carbinol group, in adenosine and 2′,3′-O-isopropylideneadenosine.

Studies on the dynamic syn‐anti equilibrium in purine nucleosides and nucleotides with the aid of 1H and 13C NMR spectroscopy

“…Syntheses of all required compounds were carried out as elsewhere described [9,11,151 (and references cited) and all were checked for purity by chromatography, spectrophotometry and by NMR spectroscopy.…”

Binding of Nucleotides and Nucleosides to Per(6‐guanidino‐6‐deoxy)cyclodextrins in Solution

“…son of chemical shifts, [12][13][14] vicinal spin-spin coupling constants, [15] 1D nuclear Overhauser enhancements, and nuclear relaxation rates, [16] as well as the effects of lanthanide cation probes (Ln 3+ ) [17] on chemical shift and relaxation rates, were analyzed. Comparison of chemical shifts indicated a dynamic syn h anti equilibrium with a preference for the anti conformation (≈70 %) in nucleosides, whereas there was a dominance for the anti conformation (virtually 100 %) in nucleotides.…”

Oligonucleosides with a Nucleobase-Including Backbone, Part 2, Synthesis and Structure Determination of Adenosine-Derived Monomers

“…Its irradiation led to a NOE of 7.8% for HÀC(3') at 5.08 ppm, and of 15% for HÀC(4') at 4.73 ppm (cf. [19]), evidencing the (5'S)-configuration of 20 and, hence, of 18. Irradiation of the propargylic HÀC(5') of 19 resonating as a doublet (J(4',5') 0.8 Hz) at 4.95 ppm led only to a NOE (14%) for HÀC(4') at 4.76 ppm, evidencing the (5'R)-configuration of 19 and 17.…”

“…Their treatment with 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) in toluene at 508 led to the anhydronucleosides 19 and 20, respectively, while NaH, as originally used for the synthesis of an 8,5'-anhydroadenosine [18] from 8-bromo-2',3'-O-isopropylideneadenosine, led to degradation (cf. [19]), presumably by initiating cleavage of the C(5')-ethynyl bond. Table 1 in Exper.…”

“…8-Unsubstituted adenosines prefer the anti-conformation, whereas 8-substituted derivatives prefer the syn-conformation, as evidenced by a downfield shift of the HÀC(2') signal [19] [32 ± 36]. The syn-conformation is also preferred by the alcohols 1 ± 3, 14, and 16 ± 18 on account of the intramolecular H-bond (see also [26] [27] [29] [32]) that directs X À C(8) close to HÀC(1').…”