Nucleosides LIII Syntheses and Reactions of 6,7-Dipyridyllumazine and 2' -Deoxylumazine N-1 Nucleosides

Abstract

SummaryThe chemical syntheses of 6,7-(a-pyridyl)-I-(lJ,5-tri-O-benzoy-~-0-ribofuranosyl)-lumazinc (6) and the corresponding free nucleoside 7 are desclibed. Thiation of 6 with P 4 SIO gave a salt type adduct derivative of 4-thiolumazine 8 which afforded the frce nucleosidc 9 on deblocking. Treatment of 8 with methanolic NHJ gave the isopterin-N-l nucleoside 10. 2,2' -Anhydro compound 13 was obtained by the diphenyl carbonate technique and characterised as the diacetate 14. Acid hydrolysis of 14 gave the arabino-nucleoside 15. which was isolated also from hydrolysis of 14 with hydroxide ion. Reaction of 7 with acetyl bromide gave the l'-bromo-2'-deoxy derivative 11 as minor product together with triacetate 12 as the main analogue. Reduction of the bromo function in 11 into the expected l'-deoxy analogue during the treatment with tri-n-butyltin hydride has failed and the 2.2' -anhydro compound 15 was the only product isolated. Alternati\·ely. the 6,7-bis-(a-pyridyl)-1-(2-deoxy-3.5-di-O-toloulyl-a and ~-D-ribofuranosyl)-Iumazine (17) and (19) were synthesized from direct condensation of sugar 16 and the silylated base 4. Debo\Cking of 17 and 19 with sodium methoxide gave the free analogues 18 and 20 respectively.

Synthesis and Biological Evaluation of New Dipyridylpteridines, Lumazines, and Related Analogues

“…Our efforts have been focused also on the synthesis of isopterin analogues as potential pharmacological compounds. Thus, heating of 5,6‐diamino‐uracil ( 22 ) with 4 in boiling ethanol afforded the lumazine 23 (45%), prepared previously in our laboratory , was converted into the 4‐thio analogue 24 (87%) on treatment with P 4 S 10 . Conversion of 24 into the amino residue was proceeded by treatment with methanolic ammonia, using autoclave (under pressure) at 120°C for 12 h to give, after purification, 27 in 56% yield.…”

“…Elution, in gradient, with methanol (0-20%) and chloroform as eluent afforded the pure product. This compound was prepared previously in our laboratory [34] from 22 (284 mg) and 4 (424 mg, 2.00 mmol). Yield: 286 mg (45%) as yellow powder, mp >300°C (dec.).…”

“…This compound was prepared previously in our laboratory from 22 (284 mg) and 4 (424 mg, 2.00 mmol). Yield: 286 mg (45%) as yellow powder, mp >300°C (dec.).…”

“…The capability of pteridines and pterines for simulating the reactivity of metal sites in several enzymes encouraged many laboratories to synthesize the metal complexes of these molecules [28][29][30]. The synthesis of various lumazine nucleosides via multi-step synthesis was a part of our program to explore such type of compounds [31][32][33][34].…”

Syntheses and properties of pterin ribonucleosides

“…Lumazine [2][3][4][5][6][7][8][9][10][11] and isopterin nucleosides 12 can be regarded as structural analogs of the pyrimidine nucleosides whereas the many pteridin-7-one N 8 -nucleosides [13][14][15][16][17][18][19][20][21][22][23] are structurally related to the purine nucleosides. The syntheses could be achieved either by a classical Hilbert-Johnson reaction 24 , the mercury salt method by Fox and Davoll 25 , the Hilbert-Johnson-Birkofer silyl procedure 26,27 or the silyl variant by Vorbrüggen 28 .…”