Abshct: Oligoribonucleotide synthesis by use of 4,4',4''-tris(4,5-dichlorophthalimido)trityl (CPTr) as a new S'-hydroxyl protecting group is described. The reaction of N-protected 2'-O(tetrahydropyran-2-y1) ribonucleosides with tris(4,5-dichlorophthalimido)trityl bromide (CPTrBr) in the presence of silver nitrate rapidly gave 5'-tritylated products 5 in high yields. Condensation of 5 with cyclohexylammonium SJ-diphenyl phosphorodithioate in the presence of mesitylenedisulfonyl chloride and tetrazole gave fully protected monomer units 6. In this study, the lactone group of uridine and the amino group of cytidine were protected with the (pivaloy1oxy)methyl and 4,4'-dimethoxytrityl groups. These new protecting groups were found to be stable upon deprotection of the CPTr group using hydrazine and removable under the usual basic and acidic conditions. Several oligoribonucleotide building blocks (7 and 8) were synthesized by selective removal of the CPTr or phenylthio group from 6 and utilized for synthesis of fully protected trimers (17, 18, and 23) containing a 3'-or 5'-terminal phosphate group and a tetramer (25). Removal of all protecting groups from the fully protected oligomers afforded AUAp, UUAp, pAUG, and CAUG. It was also found that the CPTr group could be removed by successive treatments with concentrated ammonia and with 0.01 (1 1) (a) de Rooij, J. F. M.; Wille-Hazeleger. G.; Deursen, P. H.; Serdijn, J.; van Boom, J. H. R e d . Trau. Chim. Puys-Bas 1979, 98, 537. (b) den Hartog, J. A. J.; van Boom, J. H. ibid. Red. Trau. Chim. Pays-Bas 1981,100, 275. (c) den Hartog, J. A. J.; Wille, G.; van Boom, J. H. Red. Truv. Chim. (12) (a) Levene, P. A.; Bass, M. L.