Oligonucleotide Analogues with Integrated Bases and Backbone. Part 32

Abstract

AbstractThe G[s]G dinucleoside 6 and the G[s]G* dinucleoside 8 were prepared by alkylation of the guanosine thiols derived from 2 and 5, respectively, by the C(8)‐chloromethylated guanosine 4 that was obtained from alcohol 3. Dinucleosides 6 and 8 were deacylated to 7 and 9, and fully deprotected to 10 and 11, respectively. The G[n]G dinucleoside 16 was obtained by reductive amination of aldehyde 13 with an iminophosphorane derived from azide 14 and deprotection of the resulting dimer 15. In the solid state of 6, and in a solution of 6 and 8 in CDCl3, HN(1/I) and HN(1/II) are engaged in intramolecular H‐bonds to the CO of the isobutyryl protecting groups, and HN of the isobutyryl group of unit I forms an interresidue, intramolecular H‐bond to N(7/II), leading to a syn orientation of the nucleobase at unit I, to a tg orientation of the sulfanyl moiety, and to an orthogonal orientation of the nucleobases, preventing any base pairing. The silylated and isopropylidenated dinucleosides 7 and 9 are present in DMSO solution as solvated monoplexes. Broad 1H‐NMR signals of the nucleosides 7 and 16 in CHCl3 solution evidence equilibrating G‐quadruplexes. The quadruplex formation of 7 and 16 was established by 1H‐NMR spectroscopy (only of 16), vapour pressure osmometry, mass spectrometry, and CD spectroscopy. The C(6(I))‐hydroxymethylated analogue 9 in CDCl3 and the fully deprotected dinucleosides 10 and 11 in H2O form only weakly ππ stacked associates, but no G‐quadruplexes, as evidenced by CD spectroscopy.