Adenine from 2-chloropurine

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]. ... 

Some 8-chloropurines arise from radical reactions, as with 9-substituted adenines and guanines, using dry hydrogen chloride in dimethylacetamidc combined with 3-chloroperoxy-beiizoic acid, e.g. formation of 8-chloroadenosine (5). ... 

The first synthesis of FddA (1) from 3 -deoxy adenosine derivative by Herdewijn et al. gave the fluorination product in only 10% overall yield after deprotection and purification [59]. Several years later, we also examined a similar reaction with the 5 -O-acetyl compound, but the yield was confirmed to be very poor [71]. We hypothesized that one possible reason for the low fluorination yield in the above reaction might be the nucleophilic participation of N-3 of the adenine ring, and that this might be overcome by using 6-chloropurine 3 -deoxyriboside as a starting material (see also Section 7.3.1.2.1). 

In this synthesis, a mixture of tri-0-acetyl sugars was obtained, from which the desired 2-acetamido-l,3,5-tri-0-acetyl-2-deoxy-D-ribofuranose was isolated. Another sugar, assumed to be the isomeric 2-acetamido-l,3,4-tri-0-acetyl-2-deoxy-D-ribo-pyranose, was also isolated, converted to the O-acylglycosyl chloride, and allowed to react with chloromercuri-6-chloropurine. Deblocking with dimethylamine gave a nucleoside thought to be 9-(2-acetamido-2-deoxy-oi-D-ribopyranosyl)-JV ,W -dimethyl-adenine. 

The synthetic approach to 4 -(hydroxymethyl)ribonucleosides shown in Scheme 88 is based on aldol coupling of the nucleoside-5 -aldehyde (583) with formaldehyde and accompanying Cannizzaro reduction by the excess of formaldehyde. The 2, 3 -0-methylene derivative (584) was obtained as a by-product of the reaction. The branched-chain derivative (363) (see Chapter 13) also condensed with a variety of heterocyclic derivatives e.g. 6-chloropurine and JV -benzoyl-N ,9-bis(trimethylsilyl)adenine] to give, after deacetylation, 4 -(hydroxymethyl)ribo-nucleosides. -6-Chloro-9-(5,5-dimethylfuran-2-yl)purine (585) has been synthesized using the triol (586) derived from L-glutamic acid (see Scheme 65). ... 

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