21066-33-1

Upstream product

• 752-13-6 tetra-O-acetyl riboflavin 
• 74-88-4 methyl iodide 
• 83-88-5 riboflavin 
• 69447-57-0 O^{2'_,O3'_,O4'_,O5'}-tetraacetyl-3-methyl-1,5-dihydro-riboflavin 
• 83-88-5 riboflavin 
• 752-13-6 riboflavin 2',3',4',5'-tetra-acetate 
• 132855-92-6 Acetic acid (1S,2S,3R)-2,3,4-triacetoxy-1-(4a-hydroperoxy-3,7,8-trimethyl-2,4-dioxo-3,4,4a,5-tetrahydro-2H-benzo[g]pteridin-10-ylmethyl)-butyl ester 

Downstream Products

• 28721-76-8 3-methylriboflavin 
• 69447-57-0 O^{2'_,O3'_,O4'_,O5'}-tetraacetyl-3-methyl-1,5-dihydro-riboflavin 

Relevant academic research and scientific papers

Riboflavin derivatives for enhanced photodynamic activity against Leishmania parasites

Riboflavin derivatives with various substituents (O-acyl, N-methyl, N-alkylcarboxyalkyl or N-alkyl(trialkyl)ammonium) have been prepared and spectroscopically characterized (absorption, emission and fluorescence quantum yields). Their quantum yields of photosensitized singlet molecular oxygen production (ΦΔ 0.24-0.58) and octanol/water partition coefficients (Pow ≤0.01-11) were measured. Preliminary studies indicate that all derivatives display higher phototoxicity against the human protozoan parasite Leishmania than the parent riboflavin, with negligible toxicity in the absence of light. Their photodynamic action shows a higher correlation with P;bsubesub& than with Φbsubesub&, opening up their potential application to cutaneous diseases treatment.

Synthesis and evaluation of antimycobacterial activity of riboflavin derivatives

The riboflavin biosynthetic pathway is a promising target for the development of novel antimycobacterial drugs given the lack of riboflavin transporter in M. tuberculosis. Herein, a series of riboflavin derivatives was designed, synthesized and screened for their antimycobacterial and antibacterial activity. The compounds 1a, 1b, 2a, 3a and 5a displayed noticeable antitubercular activity against M. tuberculosis with minimum inhibitory concentration (MIC99) in the range of 6.25 to 25 μM. The lead compound 5a had a selectivity index of 10.7 in the present study. The compounds 2a, 2b, 2c, 4c and 4d showed relatively low to moderate antibacterial activity (MIC = 100–200 μM) against gram-positive strains. Notably, the compounds do not show any inhibition against gram-negative strains even at 200 μM concentration. Further, molecular docking and binding experiments with representative flavin mononucleotide (FMN) riboswitch suggested that the riboflavin analogs exhibited antimycobacterial activity plausibly through FMN riboswitch-mediated repression of riboflavin biosynthesis. In addition to FMN riboswitch, flavoproteins involved in the flavin biosynthesis could also be target of riboflavin derivatives. In conclusion, the potency and low toxicity of riboflavin analogs particularly 5a (MIC99 = 6.25) make it a lead compound for the synthesis of new analogs for antimycobacterial therapy.

Azodicarboxylate-free esterification with triphenylphosphine mediated by flavin and visible light: method development and stereoselectivity control

Triphenylphosphine (Ph3P) activated by various electrophiles (e.g., alkyl diazocarboxylates) represents an effective mediator of esterification and other nucleophilic substitution reactions. We report herein an aza-reagent-free procedure using flavin catalyst (3-methyl riboflavin tetraacetate), triphenylphosphine, and visible light (448 nm), which allows effective esterification of aromatic and aliphatic carboxylic acids with alcohols. Mechanistic study confirmed that photoinduced electron transfer from triphenylphosphine to excited flavin with the formation of Ph3P+ is a crucial step in the catalytic cycle. This allows reactive alkoxyphosphonium species to be generated by reaction of an alcohol with Ph3P+ followed by single-electron oxidation. Unexpected stereoselectivity control by the solvent was observed, allowing switching from inversion to retention of configuration during esterification of (S)- or (R)-1-phenylethanol; for example with phenylacetic acid, the ratio shifting from 10?:?90 (retention?:?inversion) in trifluoromethylbenzene to 99.9?:?0.1 in acetonitrile. Our method uses nitrobenzene to regenerate the flavin photocatalyst. This new approach to flavin re-oxidation has also been successfully proved in benzyl alcohol oxidation, which is a “standard” process among flavin-mediated photooxidations.

Photocatalytic esterification under Mitsunobu reaction conditions mediated by flavin and visible light

The usefulness of flavin-based aerial photooxidation in esterification under Mitsunobu reaction conditions was demonstrated, providing aerial dialkyl azodicarboxylate recycling/generation from the corresponding dialkyl hydrazine dicarboxylate. Simultaneously, activation of triphenylphosphine (Ph3P) by photoinduced electron transfer from flavin allows azo-reagent-free esterification. An optimized system with 3-methylriboflavin tetraacetate (10%), oxygen (terminal oxidant), visible light (450 nm), Ph3P, and dialkyl hydrazine dicarboxylate (10%) has been shown to provide efficient and stereoselective coupling of various alcohols and acids to esters with retention of configuration.

Photooxidation of benzyl alcohols with immobilized flavins

Benzyl alcohols are oxidized cleanly and efficiently to the corresponding aldehydes under irradiation using flavin photocatalysts and aerial oxygen as the terminal oxidant in homogeneous aqueous solution. Turnover frequencies (TOF) of more than 800 h-1 and turnover numbers (TON) of up to 68 were obtained. Several flavin photocatalysts with fluorinated or hydrophobic aliphatic chains were immobilized on solid supports like fluorous silica gel, reversed phase silica gel or entrapped in polyethylene pellets. The catalytic efficiency of the heterogeneous photocatalysts was studied for the oxidation of different benzyl alcohols in water and compared to the analogous homogeneous reactions. Removal of the heterogeneous photocatalyst stops the reaction conversion immediately, which shows that the immobilized flavin is the catalytically active species. The immobilized catalysts are stable, retain their reactivity if compared to the corresponding homogeneous systems and are easily removed from the reaction mixture and reused. TOF of up to 26 h-1, TON of 280 and up to 3 reaction cycles without loss of activity are possible with the heterogeneous flavin photocatalysts.

Chemistry of peroxidic tetrahedral intermediates of flavin

By means of pulse radiolysis 4a-peroxy intermediates of normal and 5-alkylated flavins were produced and the kinetics of their decay into flavin and the corresponding hydroperoxide was investigated as a function of the pH. The neutral and proton-catalyzed breakdown of the 4a-intermediates of 5-alkylated flavinium cations on the one hand and of 5-protio flavins on the other was very similar. It was concluded that the rate-determining step in the neutral decomposition of normal flavin 4a-peroxides is a heterolysis along the C(4a)-O bond which is catalyzed by water as a general acid. The species initially produced consist of a N(5)-protonated flavinium cation, a neutral hydroperoxide, and a hydroxide ion. The process is completed by rapid deprotonation of the flavinium cation to yield the neutral flavin. By combination of kinetic and thermodynamic data determined in this and other laboratories, the energetics of the autoxidation of 1,5-dihydroflavin was resolved into individual steps. The proton-catalyzed breakdown of flavin 4a-peroxides is initiated by a proton-assisted expulsion of neutral hydroperoxide leaving behind the N(5)-protonated flavinium cation. The attenuation of proton catalysis with decreasing pH indicates thermodynamic protonation of the 4a-intermediates around pH 3. The site of protonation is presumably the N(5) or the N(10) atom. The hydroxide ion catalyzed breakdown of the 4a-species is best interpreted by assuming the rate-determining step to be deprotonation of the N(S)-H site followed by rapid expulsion of the hydroperoxide anion and neutral flavin. This picture demands the microscopic pKa of the N(5)-H group to be below 17. The possible role of enzymes in stabilizing the 4a-intermediates against breakdown into flavin and hydroperoxide is discussed. It is suggested that an apolar, hydrophobic pocket may be the chief stabilizing factor. In such an environment, the transition state for heterolysis and homolysis may approach each other. Finally, the bond strength of the peroxidic O-O bond was calculated from recent thermodynamic data. This bond turns out to be weaker (26 kcal/mol) than the O-O bond in any known linear peroxide. From the finding that the O-O bond is weaker than the C(4a)-O bond it is argued that, in sufficiently hydrophobic enzymes, monooxygenation may be initiated by homolysis of the O-O bond. It is suggested that the comparable strengths of the C(4a)-O and O-O bonds may be the prime reason for the versatility of flavin enzymes.