Oligonucleotide Analogues with Integrated Bases and Backbone. Part 30

• Published in: Helvetica chimica acta Vol. 96; no. 7; pp. 1235 - 1265
• Main Authors: Herdeis, Lorenz, Thomas, Siji, Bernet, Bruno, Vasella, Andrea
• Format: Journal Article
• Language: English
• Published: Zürich WILEY-VCH Verlag 01.07.2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Association; Guanosines; Hydrogen bonds; Nucleosides; Oligonucleotides; Thioethers; WatsonCrick base pairing
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.201300043

The protected G*[s]C*[s]U*[s]A*[s]U*[s]A*[s]G*[s]C* octanucleoside 24 was prepared by S‐alkylation of the thiolate derived from tetranucleoside 23 with the methanesulfonate 22, and transformed to the silylated and isopropylidenated 25, and further into the fully deprotected octanucleoside 26. Compound 22 was derived from the methoxytrityl‐protected tetranucleoside 21, and 21 was obtained by S‐alkylation of the thiolate derived from the dinucleoside 19 with methanesulfonate 17 derived from 16 by detritylation and mesylation. Similarly, tetranucleoside 23 resulted from S‐alkylation of the thiolate derived from 18 with the methanesulfonate 20 derived from 19. Dinucleosides 16 and 18 resulted from S‐alkylation of the thiolate derived from the known cytidine‐derived thioacetate 15 with the C(8)‐substituted guanosine‐derived methanesulfonates 12 and 14, respectively, that were synthesized from the protected precursors 4 and 7 by formylation, reduction, protection, and mesylation. The structures of the duplexes of 25 and 26 were calculated using AMBER* modelling and based on the known structure of the core tetranucleoside U*[s]A*[s]U*[s]A*. The former shows a helix with a bent helix axis and strong buckle and propeller twists, whereas the latter is a regular, right‐handed, and apparently strain‐free helix. In agreement with modelling, the silylated and isopropylidenated octanucleoside 25 in (CDCl2)2 solution led to a mixture of associated species possessing at most four WatsonCrick base pairs, while the fully deprotected octanucleoside 26 in aqueous medium forms a duplex, as evidenced by a decreasing CD absorption upon increasing the temperature and by a UV‐melting curve with a melting temperature of ca. 10° below the one of the corresponding RNA octamer, indicating cooperativity between base pairing and base‐pair stacking.