31. SYNTHESIS OF POLYNUCLEOTIDES 



(C 6 H5) 3 COCH 2 , 



o 



o 



/ 



HO— P=0 



OCH 2 -°~ 



XI 



R 



Thymine 



HOCH 2 , 



<> 



115 



Thymine 



OH 



(XVII a), R = Thymine 

 (XVII b), R = Adenine 



O 



/ 

 HO— P=0 



och 2 -° 



n 



+ 



HO- 



O 



II 

 -POCH 2 ^ 



OH 



() 



\ R' 



O 



CH 3 C=0 



(XIV a), R' = Thymine 



(XIV c), R' = iV-Acetylcytosine 



(1) pec 



(2) OH 



(3) H + 



o 



/ 



HO— P=0 



OCHy/ 



K 



<) 



R' 



\| 



OH 



(XVIII), R = R' = Thymine 

 (XIX), R = Adenine 

 R' = Cytosine 



Scheme 3 



tion of products (3) extreme acid lability of glycosyl bonds in the purine de- 

 oxyribonucleosides and (4) the interference from the amino groups on the 

 adenine, guanine, and cytosine ring. 



c. Introduction of Phosphomonoester Groups at Ends of Oligonucleotide Chains 



Linear polynucleotides usually carry a phosphomonoester group at one 

 or the other end of the chain and the above methods can be adapted to yield 

 such true oligonucleotides. Two approaches are available. The first one is 

 that in which a protected phosphoryl group is used as a blocking group at 

 the outset of the synthesis. The synthesis of two dinucleotides (XX, R = 

 thymine or adenine) by this method has been recorded 8 (Scheme 4). The 

 synthesis of 5'-0-phosphoryl-thymidylyl-(3' — » 5')-thymidine (XX, R = 

 thymine) by Michelson and Todd 15 by the route illustrated in Scheme 1 

 also used the same principle. 



In the second approach the phosphomonoester end group is introduced 

 after the formation of the internucleotide bond(s) as shown below for the 

 synthesis of thymidylyl-(3' -> 5')-thymidylic-(3') acid (XXII) 21 (Scheme 



21 P. T. Gilham and G. M. Tener, Chem. & Ind. p. 542 (1959). 



