Oligoribonucleotide Synthesis. IV. Approach to Block Synthesis

A convenient block synthesis for oligoribonucleotides of predetermined sequence is developed. Preparation and deblocking of protected tetranucleotide, Ph 3 COCH 2 CO • O-U(Thp)p(Cl 3 Et)A bz (Thp)p(Cl 3 Et)U(Thp)p-(Cl 3 Et)A bz (Thp)-OH (8) to give UpApUpA is described. Phosphorylation of HO-U(Thp)-OH derivative (1; R = Ph 3 COCH 2 CO) and subsequent coupling with HO-A bz (Thp)-OH (4) gave protected UpA (5). Specific removal of triphenylmethoxyacetyl group from 5 is accomplished by dilute methanolic ammonia. 5′-Hydroxyl group of resulting UpA derivative (7) is condensed with the 3′-phosphate derivative of 5 to give 8 in good overall yield.Ease of mild alkaline cleavage, convenient ceric sulfate spray detection and enhancement of solubility, make the triphenylmethoxyacetyl group an excellent choice for 5′-protection of nucleoside derivatives.