Ribo-oligonucleotides, synthesis

Trichloroethanol has been used as a protecting group in the triester approach for the synthesis of deoxyribo- [29] as well as ribo-oligonucleotides [30]. It can be removed selectively by reduction with Zn or Zn/Cu, as previously discussed. The triesters may be synthesized either by stepwise addition of the two properly protected nucleosides to, , -trichloroethyl phos-phorodichloridate (Fig. 6.11a) or by condensation of a/3, 3, 3-tri-chloroethyl ester of a nucleotide with a nucleoside using an arylsulphonyl chloride as a condensing agent (Fig. 6.11b). 

The jS-cyanoethyl group has been employed for the protection of phosphate diesters in the synthesis of deoxyribo- [34] and ribo-oligonucleotides [35]. It is introduced using a procedure similar to Fig. 6.11b, and is selectively removed on treatment wdth sodium hydroxide. In the synthesis of ribo-oligonucleotides protection by the phenyl group, also alkali-labile, has been described [36] (Fig. 6.14). It is introduced as in Fig. 6.11a. 

Figure 54. UV- jectroscxqMcally detomined melting curve of the p-RNA duplex p-Ribo(Ag) -Ribo(Ug). The curves shown by flie p-Ribo(Ag) and p-Ribo(Ug) strands before mixing demonstrate there is no adenine-adenine self-pairing in p-RNA, in sharp contrast to homo-DNA (cf. fig. 18 in lecture 1). For the synthesis of p-RNA oligonucleotides see [8].

Another area that has recently kindled a considerable effort in solution synthesis relates to branched oligonucleotide chains. Although such structures previously were postulated as byproducts of phos-phodiester oligonucleotide condensations and have occasionally been prepared as deoxytrinucleoside monophosphates (43,126,127), branched oligonucleotide structures have gained much interest in the ribo series because of the discovery of lariats as intermediates in the process of intron splicing (see references in 128-131). 

---