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Oligonucleotide Analogues with Integrated Bases and Backbone. Part 32
Author(s) -
SchulzeAdams Martina,
Bernet Bruno,
Touboul David,
Egli Daniel,
Herdeis Lorenz,
Vasella Andrea
Publication year - 2014
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201400175
Subject(s) - chemistry , nucleobase , moiety , intramolecular force , reductive amination , guanosine , vapor pressure osmometry , piperidine , dimer , stereochemistry , nuclear magnetic resonance spectroscopy , guanine , alkylation , medicinal chemistry , organic chemistry , nucleotide , dna , biochemistry , vapor pressure , gene , catalysis
The 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 CDCl 3 , HN(1/I) and HN(1/II) are engaged in intramolecular H‐bonds to the CO 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 1 H‐NMR signals of the nucleosides 7 and 16 in CHCl 3 solution evidence equilibrating G‐quadruplexes. The quadruplex formation of 7 and 16 was established by 1 H‐NMR spectroscopy (only of 16 ), vapour pressure osmometry, mass spectrometry, and CD spectroscopy. The C(6(I))‐ hydroxymethylated analogue 9 in CDCl 3 and the fully deprotected dinucleosides 10 and 11 in H 2 O form only weakly π π stacked associates, but no G‐quadruplexes, as evidenced by CD spectroscopy.