FRANK M. HUENNEKENS 



bridge undertook a systematic and compreliensive program 

 directed toward the chemical synthesis of mono- and dinucleo- 

 tides and related substances. In addition to their contributions 

 to the fundamental chemistry of nucleotides and phosphate 

 esters, some of their monumental achievements include the total 

 synthesis of: (7) purines and pyrimidines; (2) various ribo- and 

 deoxyribonucleosides (demonstrating, in passing, that the sugar 

 moieties were joined by |3-glycoside linkages at the 3' and 9' 

 positions of the pyrimidines and purines, respectively) ; (3) 

 AMP, ADP and ATP, FMN and nicotinamide riboside; (4) 

 the 2', 3', and 5' mononucleotides of the purines and pyrimi- 

 dines; and finally, (5) the dinucleotides, UDPG and FAD. 

 The latter feat, which represented the first total synthesis of a 

 dinucleotide, deserves a word of additional comment. It was 

 carried out by condensation of the two key substances : 



O O 



Riboflavin— O—P—Oi A? + CI 



-P— O Adenosine (isopropylidine) 



OH OBz (14) 



followed by removal of the protective benzyl (Bz) and isopro- 

 pylidine groups. 



Chemical syntheses of nucleotides are costly at present and 

 attended by relatively low yields (cf., however, Khorana's 

 synthesis of adenosine and uridine polyphosphates (25)), and it 

 is doubtful whether they can compete commercially with isola- 

 tion procedures until these difficulties are overcome. However, 

 the value of this approach lies first in that it provides unambig- 

 uous proof of structure (sometimes lacking in the original as- 

 signment of structure to a coenzyme), and secondly in that it 

 provides routes to otherwise unavailable coenzyme analogues or 

 even to those coenzymes whose isolation from natural sources is 

 not readily feasible. 



Perhaps the successful efforts of Todd in this area and the 

 dramatic demonstration by Lynen (30) that the mystical "active 

 acetate" is, in reality, a straightforward organic substance, 



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