N-substituted purines

The N-3 resonance is always 20-30 ppm more shielded in N -substituted compounds than in the comparable N -isomers. This feature has been used together with the characteristic three-bond H- C coupling pathways to study the structures of various N-substituted purine derivatives. Very recently, an identical approach has been used to determine the position of alkylation for several purine derivatives reacted with... 

N-Substituted Purines with Non-coordinating Pendant Arms. 149... 

N-Substituted Purines with Potential Chelating Pendant Arms. 150... 

All these steps proceed to afford free or N -substituted crystalline cytidines 6 in high yields [11] (cf. the preparation of N (tetramethylene)cytidine 6b in 95.4% yield in Section 1.1.). This simple one-pot reaction is also very easy to perform on a technical scale, as are the subsequently discussed analogous silylation-aminations of purine nucleosides and other hydroxy-N-heterocycles (cf. Sections 4.2.4 and 4.2.5). The concept of silylation-activation while simultaneously protecting hydroxyl groups in alcohols, phenols, or phosphoric acids by silylation was subsequently rediscovered and appropriately termed transient protection [16-18]. 

In a review, Moreland, et aj. (11) reported that thiourea, al-lylthiourea, D-xylulose, sodium diethyldithiocarbamate, L-methionine, n-propyl-di-n-propylthiolcarbamate, twelve 6-(substituted) purines, and two coumarin derivatives stimulated Stri qa seed germination. 

Predictably, 1,2,4-triazole is alkylated preferentially at the 1-position [36, 38,39]. Specific alkylation at the 4-position can be achieved by the initial reaction with dibromomethane to form the bis-triazol-l-ylmethane (see below), followed by quat-emization of the triazole system at the 4-position and subsequent C-N cleavage of the 1,1 -methylenebistriazolium salts [40]. 1,2,3-Benztriazole yields a mixture of the isomeric 1- and 2-alkylated derivatives [41]. The 1-isomer predominates, but the ratio depends on whether the reactions are conducted in the presence, or absence, of a nonpolar organic solvent (Table 5.33). Higher ratios of the 1-isomer are obtained under solidrliquid two-phase conditions. Thus, alkylation of 1,2,3-benztriazole with benzyl chloride produces an overall yield of 95% with the l- 2-isomer ratio of ca. 5.7 1 similar reactions with diphenylmethyl and triphenylmethyl chlorides gives overall yields of 95% (9 1 ratio) and 70% (100% 1-isomer), respectively [38], 6-Substituted purines are alkylated at the N9-atom and reaction with 1-bromo-3-chloropropane yields exclusively the 9-chloropropyl derivative (cf. reaction wi phenols) [42]. 

This enzyme ]EC 4.2.99.13], also known as lupinic acid synthase, catalyzes the reaction of O-acetyl-L-serine with zeatin to produce lupinate and acetate. Zeatin is N -(4-hydroxy-3-methyl-butyl-iran5 -2-enylamino)purine. A number of other A -substituted purines can function as substrates for this enzyme. 

X., Schultz, P. G. (2002) Resin-capture and release strategy toward combinatorial libraries of 2,6,9-substituted purines. J Comb Chem 4, 183-186. (b) Ding, S., Gray, N. 

Some other examples of application of 15N NMR spectroscopy include establishing the protonation site of A2-pyrazolines (87MI301-01) and assigning the structures to isomeric N-7 and N-9 substituted purines (86T5073). 

In 1993 free-radical formation in adenosine and some pyrimidines was investigated by ESR spectroscopy after bombardment with heavy ions at 100 K <93MI 711-02). Spectra were observed at 77 K, after irradiation at 100 K, upon annealing to 300 K and storage at 300 K. Individual radical patterns were isolated from the spectra by computer manipulation and assigned to structures by powder simulation based on literature data. Adenosine exhibits two H-addition radicals at C-2 and C-8. Reactions of C-6 and N-9 substituted purines with OH radicals have been studied by pulse radiolysis <87JPC4138>. 

Imidazole (basic pK 7, i.e. N NH ) is much more basic a molecule than pyrimidine (basic pK 1.31) and the combination of the rings in purine results in a basic pK of 2.39. Since the basicity of purine is depressed by electron-withdrawing groups such as trifluoromethyl and since the decrease in basicity is greatest with the 6-substituted purine. 

A series of new substituted purin-6-ones 2 have been prepared by heating ethyl 4-acyl-aminoimidazole-5-carboxylates with primary amine hydrochlorides and phosphorus pentoxide in N,N-dimethylcyclohexylamine. ... 

Similarly, adenosine, inosine and 2 -deoxyinosine have been converted into their 8-trifluoromethyl derivatives by reaction with the copper complex formed from trifluoromethyl iodide and copper in hexamethylphosphorotriamide (80JCS(P1)2755>. N -Trifluoromethyl-purine riboside was also produced from 6-chloropurine riboside. Recently, guanosine has been shown to give the C(8)-substituted derivative (148) by reaction with a benz[a]anthracene 5,6-dioxide at pH 9.5 over 4 days at 37 °C (80CC82>. 

A daring expedient to obtain the right starting material was the alkaline cleavage of a similarly substituted purine (0.5 N NaOH, room temp, 1 h) to give 6-chloro-5-formamido-4[(2,3-0-isopropylidene-D-ribofuranosyl)-amino]pyrimidine, from which the formyl group was removed by acid hydrolysis, followed by formation of the triazole ring with aqueous nitrous acid (optical purity was retained). ... 

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