Oro: Experimental Organic Cosmochemistry 473 



in smaller yields from aqueous solutions of formaldehyde and acetaldehyde in 

 the presence of calcium oxide.^-^ 



Synthesis of Purines and Purine Intermediates 



The formation of purines on the primitive Earth or in cosmic bodies pose^ 

 a priori a difficult conceptual problem because it requires the formation of two 

 fused heterocyclic structures, an imidazole and a pyrimidine. 



In principle, there are, however, two relatively simple mechanisms or path- 

 ways which can be visualized for the formation of the purine ring. One involves 

 condensation of a 3-carbon compound with a 1-carbon reactant to form a 4,5- 

 disubstituted imidazole and the other involves condensation of a C3 compound 

 with a Ci reactant to form a 4,5-disubstituted pyrimidine. The reaction 

 terminates by cyclization of either the disubstituted imidazole or the disubsti- 

 tuted pyrimidine with another mole of the Ci reactant. 



It is known that the formation of purines in living organisms occurs by a 

 pathway involving 4,5-disubstituted imidazole derivatives,^-'' and it has also 

 been observed that the acid degradation of adenine yields 4-aminoimidazole-5- 

 carboxamidine as an intermediate.'-^ On one hand we have the very mild 

 conditions of enzymatic synthesis and on the other hand the very drastic 

 conditions of acid hydrolysis, yet in both cases a 4,5-disubstituted imidazole 

 shows as an intermediate. Shortly after these observations were made it 

 became apparent to the author that if a nonenzymatic synthesis of purines 

 under possible primitive Earth conditions was discovered, it may likely proceed 

 through the imidazole pathway. The first demonstration of the spontaneous 

 synthesis of adenine from hydrogen cyanide under conditions presumed to 

 have existed on the primitive Earth was made relatively recently in our labora- 

 tory,^^* and in line with the above reasoning 4,5-disubstituted imidazoles were 

 found in the reaction product as intermediates. 



Adenine was synthesized in substantial amounts by heating a solution of 

 hydrogen cyanide (1 to 15 m) in aqueous ammonia for 1 or several days at 

 moderate temperatures (27 to 100°). The insoluble black polymer of hydrogen 

 cyanide was removed by centrifugation and adenine was isolated from the 

 red-brown supernatant solution by chromatographic methods. The main 

 ultraviolet absorbing compound of the reaction product was identified as 

 adenine by a number of different procedures including ultraviolet spectro- 

 photometry and the melting point of its picrate derivative. The synthesis was 

 found linear with time at room temperature, and in a typical experiment at the 

 end of 4 days more than 100 mg. of adenine per liter of reaction mixture were 

 obtained.^'^^ 



Since adenine is an essential building block of nucleic acids and of the most 

 important coenzymes, and since hydrogen cyanide, ammonia, and water are 

 presumed to be common natural constituents of the solar system, these findings 

 were considered to be of special significance in relation to the problem of the 

 origin of life. 



In addition to adenine several purine precursors, namely 4-aminoimidazole- 

 5-carboxamide (AICA), 4-aminoimidazole-5-carboxamidine (AICAI), form- 

 amide, and formamidine were also found in the reaction product.'^^'^^' The 



