Chloropurines

When 6-chloropurine is heated with aqueous sodium hydroxide, it is quantitatively converted to hypoxanthine. Suggest a reasonable mechanism for this reaction. 

The use of m-chloroperbenzoic acid and HC1 in an aprotic solvent was reported for preparing 2-chloropurine nucleosides (81JOC2819). 

In a follow-up article, the authors have shown that, in addition to 2-iodopurines, fluoro and chloropurines can also be rapidly aminated imder microwave-promoted conditions [186]. The conversion levels indicated that both fluorine and iodine were better choices than chlorine as the C-2 substituted halogen. 

A convenient synthesis of 6-cyanopurines from A-THP protected 6-chloropurines is that shown in Scheme 16. This method should be applicable to other chloro nitrogen heterocycles <95CCC1386>. 

Benzy 1-6-chloropurine reacts with tetrakis(triphenylphosphine)palladium in DCE to give, not only the 6-purinylpalladium(Il) complex 102, but a dinuclear complex 103. Using Stille coupling (RSnBus) only the 6-substituted purine is obtained <96ACS462>. 

The general scheme for preparation of the alkylated adenosine and deoxyadenosine involved the interaction of the appropriate amino-hydrocarbon with a 6-chloropurine riboside (116). This allowed for the most specific interaction without too many byproducts. The molecular structures determined from diffraction studies are shown in Figures 24 and 25. In Figure 24 the shape of an alkylated nucleoside (115) is compared with that of the unalkylated form,... 

Tominaga, M Konishi, K. Aida, T. Catalysis of Nudeo-base via Multiple Hydrogen-Bonding Interactions Accderation of Aminolysis of 6-Chloropurine Derivatives by Uradls J. Am Chem Soc 1999,121,7704-7705. 

Ci3H19ClN405S l-(6-Chloropurin-9-yl) -1-S-ethyl-l-thio-D-glycero-D-ido-hexitol (CLPTGL10)82... 

Unsaturated monosaccharides [e.g. (91)] react with the Ph3P-DAD combination in the presence of phthalimide, with inversion of configuration of C-4, to form the phthalimido-derivatives (92).82 Treatment of carbohydrates having a free anomeric OH group with 6-chloropurine, DAD, and methyldiphenylphosphine gives the purine nucleosides (93).83... 

Dichloroanthaquinones have also been converted into the corresponding dicyano derivative, via what has been claimed to be the disulphonic acid (vide supra) [76]. Chloropurines have been converted into the corresponding cyano compounds using tetraethylammonium cyanide [77]. 

Even when a leaving group is present on position C-2, no addition at C-2 takes place. Another example to illustrate this behavior can be taken from the reaction of 2,6-dichloropurine with potassium amide in liquid ammonia. Besides 2-chloroadenine, 2,6-diaminopurine was obtained (81TH1). It was proved that the 2,6-diaminopurine was not formed from 2-amino-6-chloropurine but from 2-chloroadenine (Scheme 11.40A). 

The ribonucleotides of 6-mercaptopurine, 6-thioguanine, 6-chloropurine, and purine have been prepared chemically for biochemical investigations [138-141 ]. 

Adenine aminohydrolase has been found in micro-organisms, but not in mammalian cells, and the substrate specificities of the enzymes from Azotobacter vinelandii and Candida utilis were found to be similar [55, 56], Among other purines, 2-aminoadenine, A -aminoadenine, and 6-chloropurine were found to be substrates [55]. ... 

Chloropurine ribonucleotide and thioinosinic acid also react covalently with GMP reductase, the enzyme that converts guanylic acid to inosinic acid and ammonia [318]. 

The significance of these in vitro enzyme inhibition studies is uncertain, in view of the evidence that has been presented concerning the sensitivity of cancer cells to feedback inhibition by these nucleotides. On the other hand, 6-chloropurine inhibits the de novo biosynthesis of nucleic acid guanine but not of nucleic acid adenine in sarcoma 180 ascites cells [319],... 

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