Heterocyclic Chemistry at a Glance

Purines 131

Synthesis of purines from 5-aminoimidazole-4-carboxamide

(1,2- and 2,3-bonds made)

5-Aminoimidazole-4-carboxamide (usually known by the acronym AICA) and its riboside are commercially available
and are the best starting materials for the preparation of 2-substituted hypoxanthines and inosines, respectively. Adenine
derivatives can also be prepared by a very similar route, employing the corresponding aminoimidazole-carbonitriles.
(AICA riboside is the biosynthetic precursor to inosine.)

‘One-step syntheses’

The formation of purines, such as adenine, in the ‘primordial soup’ was probably a pre-condition for the evolution of
life! Amazingly, relatively complex molecules such as adenine can be formed by the sequential condensation of very
simple, fundamental molecules such as ammonia and hydrogen cyanide. Adenine, C 5 H 5 N 5 , is formally a pentamer
of hydrogen cyanide and indeed can be prepared in the laboratory by reaction of ammonia with hydrogen cyanide,
although not with great effi ciency. An equivalent, but more practical, method involves dehydration of formamide.

Exercises

1. What are the structures of the intermediates and fi nal product of the following sequence: guanosine
   2 ,3,5-triacetate reacted with POCl 3 → C 16 H 18 ClN 5 O 7 then this with t-BuONO–CH 2 I 2 → C 16 H 16 ClIN 4 O 7 ,
   this product with NH 3 –MeOH → C 10 H 12 IN 5 O 4 and fi nally this compound with PhB(OH) 2 –Pd(PPh 3 ) 4 –
   Na 2 CO 3 giving C 16 H 17 N 5 O 4. How could this same purine be prepared from AICA-riboside in four steps?


2. Suggest a sequence for the transformation of adenosine into 8-phenyladenosine.


3. Give structures and explain the following: adenosine with Me 2 SO 4 → C 11 H 15 N 5 O 4 , this with aq. HCl pro-
   duces C 6 H 7 N 5 , and fi nally aq. NH 3 on this last compound gives an isomer, C 6 H 7 N 5.


4. Write structures for the purines produced by the following reactions: (i) heating 4,5,6-triaminopyrimidine
   with formamide; (ii) treating 2-methyl-4,5-diaminopyrimidin-6-one with sodium dithioformate, then
   heating (in quinoline).