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Nucleotides. Part LIV . Synthesis of condensed N 1 ‐(2′‐deoxy‐β‐ D ‐ribofuranosyl)lumazines, New fluorescent building blocks in oligonucleotide synthesis
Author(s) -
Rosler Angelika,
Pfleiderer Wolfgang
Publication year - 1997
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.19970800611
Subject(s) - chemistry , nucleobase , oligonucleotide , oligonucleotide synthesis , stereochemistry , stacking , anomer , nucleotide , monomer , fluorescence , crystallography , dna , organic chemistry , polymer , biochemistry , gene , physics , quantum mechanics
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 N 1 ‐(2′‐deoxyribonucleosides) 15 – 21 . The β‐ D ‐anomers 15 , 17 , 19 , and 21 were deblocked to 24 – 27 and, together with N 1 ‐(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‐cyanoethyI 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.