Synthesis of hexopyranosyl pyrimidine homonucleosides

Synthesis of 1,2,3‐Triazole‐Linked Hexopyranosylpyrimidine Nucleosides and Their Application as Hepatitis B Viral DNA, HBsAg and HBeAg Suppressants

“…Structures of all synthesized intermediates and targeted 1,2,3‐triazole linked novel hexopyranosyl mono/double‐headed pyrimidine nucleosides, i. e ., 10 , 11 , 12 , 13 a – b , 14 a – b , 15 a – b , 16 , 17 , 18 , 19 a – b , 20 a – b were unambiguously established on the basis of their spectral ( 1 H, 13 C NMR, IR spectra and HRMS) data analysis. Structures of the known compounds, i. e ., 10 , 11 , 16 and 17 were further confirmed by comparison of their spectral data with those reported in the literature [31–32] …”

“…The sugar precursor for the synthesis of 1,2,3‐triazole linked double‐headed nucleosides 19 a – b and 20 a – b was ditosylated derivative 17 which was synthesized as a result of treatment of dihydroxy 2,6‐anhydro‐heptitol 16 with three equivalents of tosyl chloride in pyridine in 90 % overall yield [31–32] . The ditosylated derivative 17 was reacted with three equivalents of sodium azide in DMF and resulted diazido glucoheptitol 18 was reacted with N 1‐propynylated pyrimidines 13 a – b in a similar fashion via Copper‐Catalyzed Azide‐Alkyne Cycloaddition (CuAAC) using the above reaction conditions to afford tri‐ O ‐benzylated bis(1,2,3‐triazole) nucleosides 19 a – b in 72 % and 78 % yields respectively (Scheme 2).…”

Double-headed nucleosides: Synthesis and applications

“…Žinić and co-workers [59] synthesized 5′-(5-iodouracil-1yl)uridine ( 85), 5′-(5-iodouracil-1-yl)-5′-deoxyadenosine (86) and 5′-(uracil-1-yl)-5′-deoxyuridine (87) starting from the "reversed" 5-iodouracil-1-yl nucleoside 83 which in turn was synthesized by reacting the sodium salt of 5-iodouracil with isopropylidene-protected ribofuranoside 82 [55,59] were reacted with trifluoroacetic acid followed by acetic anhydride to afford the 1,2,3,5-tetra-O-acetyl nucleoside analogs 89a and 89b, respectively. Montgomery and Hewson base coupling reaction [60] of 1,2,3,5-tetra-O-acetyl nucleoside analogues 89a and 89b with 2,6-dichloropurine under acidic conditions resulted in the formation of mononucleoside analogs 90a,b.…”

“…Prasad and co-workers [ 86 ] synthesized hexopyranosyl double-headed pyrimidine homonucleosides 1-[(6-deoxy-6-(uracil-1-yl)-β-ᴅ-glucopyranosyl)methyl]uracil ( 200a ), 1-[(6-deoxy-6-(thymin-1-yl)-β-ᴅ-2,3,4-tri- O -benzylglucopyranosyl)methyl]thymine ( 200b ) and 1-[(6-deoxy-6-(uracil-1-yl)-β-ᴅ-mannopyranosyl)methyl]uracil ( 200c ) from dihydroxy 2,6-anhydro-3,4,5-tri- O -benzylheptitols ( 196a , b ) which in turn were synthesized from ᴅ-glucose and ᴅ-mannose [ 87 ]. The benzylated 2,6-anhydroheptitols 196a , b were reacted with tosyl chloride to form the ditosylated compounds 197a , b which upon reaction with substituted thymine and uracil 198a , b afforded the benzylated double-headed nucleosides 199a – c .…”

“…Next, debenzylation of the nucleoside monomers 199a–c afforded the final double-headed nucleoside monomers 200a–c . ( Scheme 52 ) [ 86 ].…”