31. SYNTHESIS OF POLYNUCLEOTIDES 123 



c. Polymerization of Ribonucleotides 



The specific synthesis of (C 3 '-C B ' Hoiked ribo-oligonucleotides requires 

 ribonucleotide intermediates in which the 2'-hydroxyl group is protected, 

 e.g., 2'-0-tetrahydropyranyluridine-3'-phosphate (XXX). So far, however, 

 only polymerizations to form random mixtures of C2'-C 5 ' and C 3 '-C 5 ' in- 

 ternucleotide linkages have been reported. Thus, the direct application of 

 the procedure used for polymerizing thymidine-5'-phosphate to uridine-5'- 

 phosphate gave a mixture of products whose elution pattern from cellulose 

 anion exchangers indicated that they consisted of homologous oligonucleo- 

 tides. 19 



An alternative method for the formation of random mixtures of (C2'- 

 C 6 ')- and (C 3 '-C 5 ')-linked ribo-oligonucleotides has been described. 27 This 

 involves the further activation of ribonucleoside-2' ,3 '-cyclic phosphates by 

 reaction with diphenylphosphorochloridate or tetraphenyl pyrophosphate. 



HOCH 2 ^ 0v R CH 2 /°\ R 



,>l 



O O 



P=0 



I 



o 



o o 



p 

 o o 



(C 6 H 5 0) 2 -P=0 CH,/°\ R 



(XL) \S. 



o o 

 p 

 o 



(XLI) 



The reactive species thus is the mixed anhydride of the type (XL), and the 

 tertiary esters as illustrated in (XLI) must be the initial products. These 

 would then rapidly hydrolyze 28 during work-up in any one of the three 

 possible ways to give (1) a C 2 '-C 6 ' linkage or (2) a C 3 '-C 5 ' linkage or (3) 

 a 2' ,3'-cyclic phosphate group which would form the terminus of the oligo- 

 nucleotide chain. Although there is little doubt that oligonucleotides were 

 formed in this procedure, the isolation of pure components from the mix- 

 tures and their adequate characterization has not been reported as yet. 



In conclusion, it must be emphasized that studies on chemical polymeriza- 

 tion have only begun and progress should be expected in several directions. 



27 A. M. Michelson, J. Chem. Soc. p. 1371 (1959). 



28 D. M. Brown, D. I. Magrath, and A. R. Todd, J. Chem. Soc. p. 4396 (1955). 



