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[摘要]：The (chloromethyl) cytidine 7 was obtained from alcohol 4 that was synthesized from the protected cytidine 3 by C(6)-formylation and reduction. Thioacetate 10 was obtained from the cytidine 2, and thioacetate 8 from a Mitsunobu reaction of alcohol 6. The thiomethylene-linked dinucleoside 11 was synthesized by thioether formation between the 6-(chloromethyl) cytidine 7 and the thiolate generated by S-deacetylating and N-debenzoylating the cytidine-5'-thioacetate 10. Dinucleoside 11 was desilylated to 12, and fully deprotected to 13. Similarly to 11, the C(6)-substituted analogue 14 was obtained from 7 and the C(6)-substituted 8. Stepwise deprotection of 14 provided 15-17, and complete deprotection gave 18. The thioacetylated and N-benzoylated dinucleoside 21 was obtained from the methanesulfonate 9 and the thiolate that was generated from thioacetate 8. Similarly, 7 and 8 yielded 19 that was transformed into the methanesulfonate 20. The tetranucleoside 23 was synthesized from the methanesulfonate 20 and the thiol derived from 21. It was debenzoylated to 23 and completely deprotected to 24. The partially protected dinucleosides 11, 14, and 15, and the tetranucleoside 23 pair strongly in CDCl3. The crystal structure of 11 . MeOH shows the formation of an antiparallel cyclic duplex possessing nearly orthogonal base pairs due to MeOH acting as H-acceptor from one base pair and H-donor to the other base pair. A large distance of ca. 6 angstrom between the base pairs of the cyclic duplexes was predicted by Maruzen modeling. It is corroborated by the absence of base stacking in CHCl3 solution of the duplexes formed by the (self-complementary) dinucleosides 11, 14, and 15, as evidenced by a weak temperature dependence of the CD spectra. The association constants for 11, 14, 15, and 23 were calculated from the concentration dependence of the chemical shift of H2N-C(4). No concentration dependence of the H2N-C(4) signals was observed for solutions of 23 in CDCl3, (D-6) acetone, CD3CN, (D-8)THF, (D-5)pyridine, and CDCl3/(D-6)DMSO 4 : 1. As a consequence of the strong association, the association constant for 23 had to be determined in CD3CN/(D-6)DMSO 4 : 1. The temperature dependence of the CD spectra of the fully deprotected 18 und 24, but not of 13, in H2O is rationalized by base stacking of the hydroxymethylated cytosine moieties that associate by intermolecular H-bonds of HOCH2-C(6/I) to an acceptor of unit I. The H-1-NMR spectrum of 18 and 24, but not of 13, shows a 9 : 1 mixture of the monoplex and the base-stacked duplex. |
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