Oligonucleotide Analogues with a ‘Nucleobase‐Including Backbone’. Part 10

Abstract

The dinucleoside analogues 24, 25, 28–30, and 33 associate in CDCl3 solution. Association constants, as determined from the concentration‐dependent chemical shift for HN(3) of the uridine moiety and from thermodynamic parameters, range from 265 M−1 (33) to 3220 M−1 (30). The association of 31 in CDCl3 is too strong to be determined (concentration independent δ(HN(3)) of ca. 12.8 ppm) and the fully deprotected dimer 32 proved insufficiently soluble in CDCl3. This observation strongly evidences that structural differentiation of oligonucleotides and their analogues into backbone and nucleobases is not required for pairing. The dinucleotide analogues were prepared by O‐alkylation of C(8)‐unsubstituted or of C(8)‐oxymethylated, partially protected adenosines by the C(6)‐mesyloxy‐ or C(6)‐halomethylated uridines 20–22, followed by partial or total deprotection.

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 17

“…d(HÀN(3)) for 3 extrapolated to a concentration of 0 mm is 8.5 ppm, sufficiently close to the 7.70 ppm assumed for the monoplex to conclude that the association of 3 favours the monoplex. This conclusion is in agreement with the rather low association constant (K ass ¼ 970 m À1 ), as determined by graphical analysis of the SCC [7]. The plateauforming SCC of 6 should show the strongest bending at low concentrations.…”

“…Association of the U*[o]A ( * ) Dimers. The tendency of U*[o]A ( * ) dimers to form cyclic duplexes had already been analysed on the basis of the concentration dependence of the chemical shift of HÀN(3) (shift/concentration curve, SCC) [7]. The SCCs reflect the combination of the equilibria between monoplex, duplexes, and/ or linear associates [3], while the transformation of the intermediate linear duplexes to cyclic duplexes is concentration independent.…”

“…The isopropylidenated uridine 7 was transformed into the thexyl(dimethyl)silyl (TDS; thexyl ¼ 1,1,2-trimethylpropyl) ether 8 (> 98%; Scheme 1) according to [25]. Deprotonation of 8 with excess LDA [26], followed by formylation with DMF [27] [28], hydrolysis, and reduction [29] of the resulting aldehyde [7] yielded 80% of the hydroxymethylated uridine 11. Mesylation of 11 yielded 82% of 12, while 4monomethoxytritylation gave 80% of 13 that was desilylated [30] to the alcohol 14 (84%).…”

“…Monomethoxytritylation of 21 yielded 83% of 23 that was desilylated in 82% to the alcohol 24. The association of the U*[s]A ( * ) and A*[s]U ( * ) dimers was studied by 1 H-NMR and circular dichroism (CD) spectroscopy, similarly as previously described for ethynylene- [3], (Z)-ethenylene- [5], and oxymethylene-linked dimers [7]. Vapour-pressure osmometry (VPO) was used in a few cases to determine the stoichiometry of the association.…”

“…9, c). HOÀC(5'/ II) is not involved in intermolecular H-bonding, but forms an intramolecular bifurcated H-bond to OÀC(4'/II) and O¼C(2/II) (see [7] for a similar case). As expected, both nucleobases adopt a classic syn-conformation (c ¼ 66.4 and 65.78).…”