59389-71-8

Upstream product

• 95-64-7 4-amino-o-xylene 
• 36468-53-8 β-D-ribofuranose 
• 50-69-1 D-ribose 
• 3051-94-3 3,4-dimethyl-N-ribitylaniline 
• 108-24-7 acetic anhydride 
• 36995-92-3 6-uracil 
• 111619-05-7 3,4-xylidino-D-ribofuranoside 

Downstream Products

• 57818-88-9 5-deazaflavin adenine dinucleotide 
• 19342-73-5 5-deazariboflavin 

Relevant academic research and scientific papers

Bacterial flavoprotein monooxygenase YxeK salvages toxic S-(2-succino)-adducts via oxygenolytic C–S bond cleavage

Thiol-containing nucleophiles such as cysteine react spontaneously with the citric acid cycle intermediate fumarate to form S-(2-succino)-adducts. In Bacillus subtilis, a salvaging pathway encoded by the yxe operon has recently been identified for the detoxification and exploitation of these compounds as sulfur sources. This route involves acetylation of S-(2-succino)cysteine to N-acetyl-2-succinocysteine, which is presumably converted to oxaloacetate and N-acetylcysteine, before a final deacetylation step affords cysteine. The critical oxidative cleavage of the C–S bond of N-acetyl-S-(2-succino)cysteine was proposed to depend on the predicted flavoprotein monooxygenase YxeK. Here, we characterize YxeK and verify its role in S-(2-succino)-adduct detoxification and sulfur metabolism. Detailed biochemical and mechanistic investigation of YxeK including 18O-isotope-labeling experiments, homology modeling, substrate specificity tests, site-directed mutagenesis, and (pre-)steady-state kinetics provides insight into the enzyme’s mechanism of action, which may involve a noncanonical flavin-N5-peroxide species for C–S bond oxygenolysis.

Conversion of a Dehalogenase into a Nitroreductase by Swapping its Flavin Cofactor with a 5-Deazaflavin Analogue

Natural and engineered nitroreductases have rarely supported full reduction of nitroaromatics to their amine products, and more typically, transformations are limited to formation of the hydroxylamine intermediates. Efficient use of these enzymes also requires a regenerating system for NAD(P)H to avoid the costs associated with this natural reductant. Iodotyrosine deiodinase is a member of the same structural superfamily as many nitroreductases but does not directly consume reducing equivalents from NAD(P)H, nor demonstrate nitroreductase activity. However, exchange of its flavin cofactor with a 5-deazaflavin analogue dramatically suppresses its native deiodinase activity and leads to significant nitroreductase activity that supports full reduction to an amine product in the presence of the convenient and inexpensive NaBH4.

Dibenzothiophene Catabolism Proceeds via a Flavin-N5-oxide Intermediate

The dibenzothiophene catabolic pathway converts dibenzothiophene to 2-hydroxybiphenyl and sulfite. The third step of the pathway, involving the conversion of dibenzothiophene sulfone to 2-(2-hydroxyphenyl)-benzenesulfinic acid, is catalyzed by a unique flavoenzyme DszA. Mechanistic studies on this reaction suggest that the C2 hydroperoxide of dibenzothiophene sulfone reacts with flavin to form a flavin-N5-oxide. The intermediacy of the flavin-N5-oxide was confirmed by LC-MS analysis, a co-elution experiment with chemically synthesized FMN-N5-oxide and 18O2 labeling studies.

Synthesis and electrochemical properties of structurally modified flavin compounds

Four structurally modified flavin compounds have been synthesized and characterized for their redox potential by chemical reduction with sodium dithionite. Besides the previously reported 1- and 5-deazariboflavin, a 7,8-didemethyl derivative and an 8-isopropylriboflavin have been obtained. The synthesis of these compounds started in all cases from appropriately substituted anilines that were condensed with the ribityl chain, followed by completion of the annealed three-ring structure. The didemethyl- and the isopropyl compounds gave absorption maxima similar to riboflavin (436 and 448 nm, respectively), whereas 1-deazariboflavin showed a bathochromically shifted absorption (λmax = 537 nm), and that of 5-deazariboflavin was hypsochromically shifted (λmax = 400 nm). The midpoint potentials (E0′) of the four modified flavin compounds were determined by potentiometric titration, using riboflavin as a reference compound. Both alkyl-modified flavins showed slightly less negative midpoint potentials, whereas both deaza compounds had more negative midpoint values compared to the reference compound. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Improved Chemical Syntheses of 1- and 5-Deazariboflavin

The cofactor flavin adenine dinucleotide (FAD) is required for the catalytic activity of a large class of enzymes known as flavoenzymes. Because flavin cofactors participate in catalysis via a number of different mechanisms, isoalloxazine analogues are valuable for mechanistic studies. We report improved chemical syntheses for the preparation of the two key analogues, 5-deazariboflavin and 1-deazariboflavin.

Synthesis of 5-deazaflavin adenine dinucleotide (5-dFAD) using a modified triester approach

Starting from D-ribose and 3,4-xylidine, a fifteen-step synthesis is described for the preparation of 5-dFAD (18).The synthesis involves as key intermediates, 5-deazariboflavin (8), its 2',3',4'-tris-O-(tetrahydropyranyl) derivative (12) and 2',3',4'-tris-O-(tetrahydropyranyl)-5'-O-(morpholinophosphonyl)-5-deazaribolavin (15).