A simplified and efficient route to 2'-O, 4'-C-methylene-linked bicyclic ribonucleosides (locked nucleic acid).

A novel efficient method for the synthesis of locked nucleic acid (LNA) monomers is described. The LNA 5',3'-diols containing thymine, 4-N-acetyl- and 4-N-benzoylcytosine, 6-N-benzoyladenine, and 2-N-isobutyrylguanine as nucleobases were prepared via convergent syntheses. The method is based on the use of the common sugar intermediate 1,2-di-O-acetyl-3-O-benzyl-4-C-methanesulfonoxymethyl-5-O-methanesulfonyl-D-erythro-pentofuranose (8) that easily can be prepared from D-glucose in multigram scale. Four different nucleobases were stereoselectively coupled to 8 using a modified Vorbrüggen procedure to give the corresponding 4'-C-branched nucleoside derivatives. Subsequent ring closing furnished the protected LNA nucleosides. The 5'-O-mesyl groups were efficiently displaced by nucleophilic substitution using sodium benzoate. Saponification of the 5'-benzoates followed by catalytic removal of the 3'-O-benzyl groups afforded the free LNA diols. The exocyclic amino groups of adenosine and cytidine were selectively acylated to give 4-N-acetyl- or 4-N-benzoyl-LNA-C and 6-N-benzoyl-LNA-A. The isobutyryl group of guanine was retained during the preparation of 2-N-isobutyryl-LNA-G. The LNA-T diol and base-protected LNA diols can be directly converted into LNA-phosphoramidites for automated chemical synthesis of LNA containing oligonucleotides.

Binding studies between tetrathiafulvalene derivatives and cyclobis(paraquat-p-phenylene).

The complexation between a number of different pi-electron donating TTF derivatives and the pi-electron accepting tetracationic cyclophane cyclobis(paraquat-p-phenylene) (CBPQT(4+)) has been studied by (1)H NMR and UV-vis spectroscopy. The results demonstrate that the strength of association between the donors (TTF derivatives) and acceptor (CBPQT(4+)) is strongly dependent on the pi-electron donating properties (measured by the first redox potential ) of the TTF derivatives. However, the first redox potential () is not the only factor of importance. The extended pi-surface of the TTF derivatives also exerts a stabilizing influence upon complexation. The kinetics for the complexation-decomplexation were studied using (1)H NMR spectroscopy and are related to the bulkiness of the TTF derivatives. These effects may serve to improve the design of interlocked molecular systems, especially (bistable) molecular switches, in which CBPQT(4+) and a derivatized TTF unit are incorporated.