Adenine synthesis from 8-chloropurine

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. 

---