Amidines purines

Again, we ignore buried amidines such as imidazoles and purines, and note the only such unburied amidine for which the enthalpy of formation is known to the authors is the above jV,jV -diphenylformamidine. (There are some guanidine derivatives for which the enthalpies of formation are known, but these seem inappropriate to use, much as carbonates and carbamates are not usually considered normal carboxylates.)... 

The readiness of amidine formation in reactions of lactim ethers with amines has been used in the synthesis of 8,9-poly methylene-purines.97 Attempts to condense 2 (R = Me) with uramil and l,3-dimethyl-4,5-diaminouracil failed.97 Lactim ethers were also found not to react with derivatives of 5-aminouracil, probably due to the low basicity of the latter.97... 

Amidino and amino groups are converted in high yield into a fused pyrimidine ring on stirring the compound with (in this example, labelled) acetic formic anhydride (review of this compound [3823]. Amidino-nitriles react with either ammonium acetate or methylamine to give fairly good yields of the amino-pteridines (reviews of pteridines [3454, 3594, 3669]). Formic acid provides a carbon atom to complete the pyrimidine ring of a purine in this example of cyclization of an amino-amidine [2431]. No additional atoms are needed in the cyclization of the pyrazine (43.1) to a dihydropteridine [2159]. 

Arnold L, Tocik Z, Bradkova E, Hostomsky Z, Paces V, Smrt J. Automated chloridite and amidite synthesis of oligodeoxyribonucleotides on a long chain support using amidine protected purine nucleosides. Collect Czech Chem Commun 54 523-532, 1989. 

The dihydroimidazo[l,5-fl]-l,3,5-triazepines (54) can also be prepared in good yields by the treatment of 5-amino-l-[2-(ethylamino)ethyl]imidazoles (53) with triethyl orthoformate. It should be noted that the reaction of triazepines (M) with ammonia resulted in ring opening to exocyclic amidines, which would subsequently undergo alternative cyclization to give purines (55) and (56), respectively (Scheme 8) <91S822>. 

These antibiotics, which show antitumour activity, strongly inhibit the synthesis of purines in liver extracts and cause the accumulation of the formyl derivative of A -glycylribosylamine 5-phosphate (LIX). Under normal conditions the latter reacts with glutamine and ATP, in the presence of a liver enzyme, to form the amidine LX. Buchanan has shown that azaserine (XXIX) and DON (XXX) inhibit this reaction specifically, by competing with glutamine for the enzyme sitei s. After combining with the enzyme the... 

Reaction of 848 with amino heterocycles is a valuable approach to chain-fluorinated purines and their bioisosteres. It was found that cyclocondensation of 848 with electron-rich aromatic and heteroaromatic amines proceeded in two steps (Scheme 191) [543, 551-554]. First, amidines 913 were formed under mild conditions (EtgN, CH2CI2, ambient temperature) in moderate yields (44-60 %). Cyclization of 913 occurred under harsh conditions (toluene or xylene, reflux) however, the yields of the products 914 in this step were high (83-96 %). It should be noted that in the case of 5-methyhsoxazol-3-amine 915, triazine derivative 917 was formed instead of the corresponding pyrimidine [555]. 

The antibiotic azaserine (O-diazoacetyl-L-serine), which is used as a sequential blocking agent in the chemotherapy of cancer, is a structural analogue of glutamine and hence interferes with the biosynthesis of the purine nucleus at one of the earliest stages amidine formation (Buchanan,... 

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