Nitrofurans types

Type 1 are 02-insensitive six-electron reductases that catalyze the sequential reduction of nitroarenes to nitroso, hydroxylamino, and amino arenes. They are encoded in E. coli by NfsA for the major enzyme and NfsB for the minor (Rau and Stolz 2003), and are also important in establishing resistance to nitrofuran drugs (Koziarz et al. 1998). 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

On the other hand, the type of the packaging material did not exert any effect on tire residue levels at a storage temperature of 20 C. At 4 C, nitrofuran residues remained stable when the egg samples were stored in glass or polypropylene tubes, but a loss of 60-70% was observed when a laminated foil was used. At 20 C, all four nitrofurans exhibited marked residue reduction, the losses being 30-50% for glass tubes, 40-60% for polypropylene tubes, and 100% for laminated foil. 

Both 2- and 3-nitrofurans with additional substituents on the available positions of the furan ring have been synthesized by cyclization procedures. The nitro-containing reagents are of type 1 or 2. No type 3 reagent seems to have been used for the synthesis of nitrofurans or condensed nitrofurans. 

The addition of Grignard reagents to 2-nitrofuran provided rra r-2,3-disubstituted 2,3-dihydrofurans as the predominant isomers <2003TL3167>. 2- and 3-(Phenylsulfinyl)furans underwent Pummerer-type reaction-initiated regioselective nucleophilic additions, as shown in Equation (20) and Scheme 13, respectively <2004OL3793>. 

Disubstituted 4//-l,2,6-thiadiazine-3,5(2//,6//)-diones (140) in the presence of piperidine readily undergo Knoevenagel type condensation with a variety of aldehydes to yield the 4-arylidene derivatives (144) (Scheme 10) <92AP(325)509>. In contrast, however, the corresponding base-catalysed condensation with 3,5-diamino-4//-l,2,6-thiadiazine-l,1-dioxide (145) is successful only with 5-nitrofuran-2-carbaldehyde (145)->(146) (Equation (13)). 

The clinically used nitrofuran compounds may be divided into four groups (1) azomethine type nitrofurans (2) di-(nitrofuran) compounds ... 

Table 6.15 lists fifty pyrimidine-containing nitrofurans of this latter type. These compounds contain a wide range of substituents at Cg and C5 of the pyrimidine ring. In addition, some compounds carry a substituent such as an alkyl group or a halogen atom on one of the carbon atoms of the butadienyl chain. 

In 1959 Skagius i synthesized similar compounds containing thiazole (Table 6.16) and thiadiazole rings (Table 6.17). Many researchers have since focused their attention on this type of compound. The following heterocyclic rings have been joined directly at Cj to the 5-nitrofuran nucleus ... 

Other Types of Nitrofurans 1. 5-Nitrofurylbutadienyl heterocyclic compounds The butadienyl derivatives, which are similar to panfuran, have been investigated and have the following formula ... 

Bryant and DeLuca (5) purified and characterized a Type I nitroreductase from Enterobacter cloacae. The protein is a monomer of approximately 27 kDa, it has a loosely bound FMN cofactor and uses NAD(P)H as an electron donor. The substrate range of the enzyme includes nitrofurans, nitrobenzenes, nitrotoluenes and quinones. The enzyme appears to produce the hydroxylamino derivative of nitroflirazone under aerobic conditions, but the product was not thoroughly characterized. Under anaerobic conditions the product is the amine. The authors did not test the effect of metals on enzyme activity, and no inhibition studies were reported. Therefore, it is not known if this enzyme is a metalloprotein. The gene encoding the Enterobacter reductase was cloned and sequenced (7). The authors found a 651 base pair open reading frame corresponding to a protein of 23.9 kDa. Comparison of the Enterobacter and Salmonella amino acid sequences revealed 88% sequence identity between the two proteins (7). 

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