Ring synthesis adenine

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). 

The A-chain is effectively an enz)une which interferes with protein synthesis by inactivating the 60S ribosomal subunit. The A-chain depurinates a specific adenine residue of the ribosomal RNA the adenine ring is hydrolysed, by the N-glycosidase action of the A-chain, when it becomes situated between two tyrosine rings in the enzyme s active site. As the ribosome is modified it can no longer act as a site of protein synthesis and this leads to the eventual death of the cell. The A-chain enzyme then moves on to deactivate another ribosome. Although only a very small proportion of the ricin molecules that enter the cell are actually moved into the cytosol, one A-chain is sufficient to destroy it. A single ricin molecule is able to deactivate more than 1500 ribosomes per minute. 

Subsequently Moyed and Magasanik ( 88) obtained the synthesis of D-er ro-imidazoleglycerol phosphate ester in cell-free preparations from three enteric bacterial species. This compound is a precursor of histidine. Evidence was also obtained that the imidazoleglycerol phosphate was formed from ribose 5-phosphate, the amide nitrogen of glutamine, and the N-1 and C-2 portion of the adenine ring of ATP. The residue of the ATP appears as 5-amino-l-ribosyl-4-imidazolecarboxamide 5 -phosphate. The latter is a well-known intermediate in purine biosynthesis and can be reconverted to ATP. This provides a cyclic process for the i thesis of the imidazole ring of histidine. 

Methyl oxetane-2-carboxylate derivatives (e.g., 284), obtained by ring contraction of aldonolactones, have been employed for the synthesis (279) of the nucleoside / -noroxetanocin [9-(/ -D-eryt/iro-oxetanosyl)adenine, 304] and its a-anomer via an a-chloride obtained by a modified Hunsdiecker reaction. Displacement of chloride by adenine and debenzylation gave 304. The threo isomer of304, /J-epinoroxetanocin (305), was likewise synthesized from D-lyxono-1,4-lactone. The oxetane nucleosides display potent antiviral activity against the human immunodeficiency virus (HIV). 

Bazzi HS, Sleiman HR Adenine-containing block copolymers via ring-opening metathesis polymerization synthesis and self-assembly into rod morphologies. Macromolecules 2002 35 9617-9620. 

The thiadiazole ring was employed as a diamine protecting group in a synthesis which led to the unambiguous formation of the 9-substituted adenine arprinocid (24) (78JOC960). The thiadiazole (23) readily underwent amine replacement, formylation, and reduction with Raney nickel to produce (24 Scheme 5). 

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