112 



H. GOBIND KHORANA 



O 







o o 



CH 3 COCH 2 /'^\ Thymine 



,N| + (C 6 H 5 0) 2 — P— O— P— OCH 2 C 6 H s > 



\ I 



1 H 



OH 



o 



CH3COCH2, 



Thymine 



O 

 0=P— OCH 2 C 6 H 5 

 H 



iV-Chloro- 

 Succinimide 



(VII) 



HOCH, 



Thymine 



O 

 CH 3 COCH 2 X°\ Thymine 



o 



I 



0=P— OCH 2 C 6 H 5 



CI 

 (VIII) 



+ 



o 



/ 



HO— P=0 

 OCH,/' 



Several 

 steps 



Thymine 



HOCH, 







Thymine 



O 

 CH 3 C=0 



OH 



(IX) 



Scheme 1 



O OOO 



II II II II 



RO— P— O- + (C 6 H a O) 2 — P— CI -> RO— P— O— P— (OC 6 H 5 ) 2 



OCH 2 C 6 H 5 OCH 2 C 6 H 5 



(X) (Xa) 



(X), (Xa), R = nucleoside radical 



to form random mixtures of d'-Ci and C 3 '-C 5 ' linked ribo-oligonucleo- 

 tides (see below). 



d. Direct Activation of Monoesters of Phosphoric Acid (Mononucleotides) 



The approach which has so far proved the most satisfactory and has been 

 used in most of the work described below, consists of the reaction of a mono- 

 alkyl phosphate (XI) and an alcohol under anhydrous conditions with di- 

 cyclohexylcarbodiimide 8 ' 17 (DCC) or reactive anhydrides such as p-tolu- 



17 H. G. Khorana, W. E. Razzell, P. T. Gilham, G. M. Tener, and E. H. Pol, /. Am. 

 Chem. Soc. 79, 1002 (1957). 



