5-aminoimidazole derivatives were considered unstable and therefore difficult to synthesize. The first non-enzymatic synthesis of 5-aminoimidazole ribotide (AIR) was only published in 1988[7] and general methodology for other examples was developed in the 1990s.[8][9]
FGAR + ATP + glutamine + H2O → FGAM + ADP + glutamate + Pi
FGAM is finally converted to AIR by the action of
AIR synthetase which uses ATP to activate the terminal
carbonyl group to attack by the nitrogen atom at the anomeric centre:
Rearrangement reactions starting from AIR incorporate portions of the molecule into additional biochemical pathways. The enzymes involved are in the
radical SAM superfamily of
iron–sulfur proteins, which use
S-adenosyl methionine as a
cofactor to initiate the conversions via
radical intermediates.[15][5]
^Bhat, Balkrishen; Groziak, Michael P.; Leonard, Nelson J. (1990). "Nonenzymatic synthesis and properties of 5-aminoimidazole ribonucleotide (AIR). Synthesis of specifically 15N-labeled 5-aminoimidazole ribonucleoside (AIRs) derivatives". Journal of the American Chemical Society. 112 (12): 4891–4897.
doi:
10.1021/ja00168a039.
^Al-Shaar, Adnan H. M.; Gilmour, David W.; Lythgoe, David J.; McClenaghan, Ian; Ramsden, Christopher A. (1992). "Preparation, structure and addition reactions of 4- and 5-aminoimidazoles". Journal of the Chemical Society, Perkin Transactions 1 (21): 2779–2788.
doi:
10.1039/P19920002779.
^Al-Shaar, Adnan H. M.; Chambers, Robert K.; Gilmour, David W.; Lythgoe, David J.; McClenaghan, Ian; Ramsden, Christopher A. (1992). "The synthesis of heterocycles via addition–elimination reactions of 4- and 5-aminoimidazoles". J. Chem. Soc., Perkin Trans. 1 (21): 2789–2811.
doi:
10.1039/P19920002789.
^Holliday, Gemma L.; Akiva, Eyal; Meng, Elaine C.; Brown, Shoshana D.; Calhoun, Sara; Pieper, Ursula; Sali, Andrej; Booker, Squire J.; Babbitt, Patricia C. (2018). "Atlas of the Radical SAM Superfamily: Divergent Evolution of Function Using a "Plug and Play" Domain". Radical SAM Enzymes. Methods in Enzymology. Vol. 606. pp. 1–71.
doi:
10.1016/bs.mie.2018.06.004.
ISBN9780128127940.
PMC6445391.
PMID30097089.
^Challand, Martin R.; Driesener, Rebecca C.; Roach, Peter L. (2011). "Radical S-adenosylmethionine enzymes: Mechanism, control and function". Natural Product Reports. 28 (10): 1709–1710.
doi:
10.1039/C1NP00036E.
PMID21779595.
^Begley, Tadhg P. (2006). "Cofactor biosynthesis: An organic chemist's treasure trove". Natural Product Reports. 23 (1): 15–18.
doi:
10.1039/b207131m.
PMID16453030.