Nucleotides. Part LIV. Synthesis of condensed N1-(2'-deoxy-β-D- ribofuranosyl)lumazines, new fluorescent building blocks in oligonucleotide synthesis

Article abstract of DOI:10.1002/hlca.19970800611

Various condensed areno[g]lumazine derivatives 2, 3, and 5-7 were synthesized as new fluorescent aglycones for glycosylation reactions with 2- deoxy-3,5-di-O-(p-toluoyl)-α/β-D-erythro-pentofuranosyl chloride (10) to form, in a Hilbert-Johnson-Birkofer reaction, the corresponding N¹-(2'- deoxyribonucleosides) 15-21. The β-D-anomers 15, 17, 19, and 21 were deblocked to 24-27 and, together with N¹-(2'-deoxy-β-D- ribofuranosyl)lumazine (22) and its 6,7-diphenyl derivative 23, dimethoxytritylated in 5'-position to 28-33. These intermediates were then converted into the 3'-(2-cyanoethyl diisopropylphosphoramidites) 34-39 which function as monomeric building block in oligonucleotide syntheses as well as into the 3'-(hydrogen succinates) 40-45 which can be used for coupling with the solid-support material. A series of lumazine-modified oligonucleotides were synthesized and the influence of the new nucleobases on the stability of duplex formation studied by measuring the T(m) values in comparison to model sequences. A substantial increase in the T(m) is observed on introduction of areno[g]lumazine moieties in the oligonucleotide chain stabilizing obviously the helical structures by improved stacking effects. Stabilization is strongly dependent on the site of the modified nucleobase in the chain.