CHEMISTRY OF NUCLEOSIDES AND NUCLEOTIDES 



173 



nucleoside-5'-phosphates, the cyclic phosphates, and the pyrimidine deoxy- 

 ribonucleoside diphosphates. Successful methods employ unequivocal pro- 

 tection of appropriate hydroxyl groups on the sugar residue, then phos- 

 phorylation and removal of protecting groups. 



a. The 5' -Phosphates 



The most convenient derivatives for the synthesis of ribonucleoside-5'- 

 phosphates are the 2',3'-isopropylidene compounds. For example inosine- 

 5'-phosphate was first synthesized from 2',3'-isopropylidene inosine by 

 phosphorylation with phosphoryl chloride in pyridine, then removal of the 

 isopropylidene residue by cautious acid hydrolysis.^'' 



OH 



— — 



MeCMe 



/\ 







CH-CH-CH-CH-CHrOH 



N 



-0- 



OH 



MeCMe 



/\ 

 O O 



L-CH-CH-CH-CH-CH.-OPOsH, 



I 



N 



A synthesis of adenosine-5'-phosphate from 2', 3 '-isopropylidene adeno- 

 sine follows similar lines. ^^ The overall yield in this synthesis is low, how- 

 ever, and the final product difficult to purify. Similarly, phosphorylation 

 of 2',3'-diacetyladenosine with phosphoryl chloride, then removal of acetyl 

 groups with alkali, gives only low yields of adenosine-5'-phosphate.'** 



The difficulties in these syntheses are probably associated with the nature 

 of the phosphorylating agent. The simultaneous formation of mono-, di-, 

 and triesters and subsequent difficulties arising in the hydrolysis of the 

 phosphorochloridates may be avoided by use of dibenzyl phosphorochlori- 

 date.^^* Thus, 2',3'-isopropylidene adenosine reacts readily with dibenzyl 

 phosphorochloridate in pyridine to give the 5'-dibenzyl phosphate. Benzyl 



-O- 



MeCMe 



/\ 

 OCH.Ph 



I 

 '-CH-CH-CH-CH-CH.-OP = 

 I ■ I 



N. ^N\ OCHaPh 



X Hj/Pd 



NH, 



N 



NH, 



O — 



MeCMe 



CH-CH-CH-CH-CH^-OPOjH, 



I 



N 



2',3'-Isopropylidene adenosine-5'- 

 dibenzyl phosphate 



'^8 F. R. Atherton, H. T. Openshaw, and A. R. Todd, /. Chem. Soc. 1945, 382. 



