SYNTHESIS OF 5-PHENYL-2(1H)-PYRIMIDINONE NUCLEOSIDES

Reaction of 2-phenyltrimethinium salt 1 with thiourea and subsequent r eaction with chloroacetic acid afforded 5-phenyl-2(1H)-pyrimidinone (3 ). Its silyl derivative 4 was condensed with 1-O-acetyl-2,3,5-tri-O-be nzoyl-D-ribofuranose under catalysis with tin tetrachloride or trimeth ylsilyl trifluoromethanesulfonate to give protected nucleoside 3 toget her with nosyl)-6-hydroxy-5,6-dihydro-2(1H,3H)-pyrimidinone (7). The g reatest amounts of 7 were formed with the latter catalyst. Nucleosidat ion of the silyl derivative 4 with protected methyl 2-deoxy-D-ribofura noside 8 or 2-deoxy-D-ribofuranosyl chloride 9 afforded -toluoyl-beta- D-ribofuranosyl)-5-phenyl-2(1H)-(10) and its alpha-anomer II. Reaction of 10 and 11 with methanolic ammonia gave free 7'-deoxynucleosides 12 and 13, Compound 13 was converted into 5'-O-tert-butyldiphenylsilyl-3 '-O-mesyl derivative 14 which on heating with 1,8-diazabicyclo[5.4.0]u ndec-7-ene (DBU) and subsequent cleavage with tetrabutylammonium fluor ide afforded 2',3'-dideoxy-2',3'-didehydronucleoside 15. Reaction of t he silyl derivative 4 with 1,2-di-O-acetyl-3,5-di-O-benzoylxylofuranos e (18), catalyzed with tin tetrachloride, furnished O-benzoyl-beta-D-x ylofuranosyl)-2(1H)-pyrimidinone (19) which was deprotected to give th e beta-D-xylofuranosyl derivative 22. As a side product, the nucleosid ation afforded the beta-D-xylopyranosyl derivative 23. Deacetylation o f compound 19 gave -beta-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidinone (24) which on reaction with thionyl chloride afforded 2'-chloro-2'-deo xynucleoside 25 and 2',O-6-cyclonucleoside 26. Heating of compound 25 with DBU in dimethylformamide furnished the lyxo-epoxide 27 which on r eaction with methanolic ammonia was converted into free -beta-D-lyxofu ranosyl)-5-phenyl-2(1H)-pyrimidinone (28). Reaction of tyl-5-O-benzoyl -3-O-methanesulfonyl-D-xylofuranose (30) with silyl derivative 4 gave the nucleoside 31 which by treatment with DBU was converted into an eq uilibrium mixture of 5'-benzoylated arabino-furanoside 33a and its 2', 6-anhydro derivative 33b.