Sulfonamides derivatization

The sulfonamide-derivatized support is readily prepared by treating amino-methylated resin with 4-carboxybenzenesulfonamide, N,N-diisopropylcarbodi-imide, and 1-hydroxybenzotriazole. Treatment of the sulfonamide resin with pentafluorophenyl active ester of 4-bromophenylacetic acid and 4-(dimethyl-amino) pyridine then gives the acylsulfonamide. Subsequent treatment of acylsulfonamide with excess LDA (15 equiv) in THF at 0 °C results in rapid deprotonation to give the trianion. 

Methodologies to produce reactive SAMs, such as inter-chain anhydrides, have been adapted to forming patterns of SAMs with pCP (45-47). Monolithic films of SAMs containing reactive pentafluorobenzyl esters were converted into patterned amides by using a stamp containing a primary amine. In the areas of contact, the amine reacts with the activated surface to form a patterned amide. Printing of benzenesul-fonamide was detected by binding cabonic anhydrase (CA) to the sulfonamide-derivatized SAM. Benzenesul-fonamide binds to CA with a dissociation constant of less than 10 M. Similarly, the stamp can be treated with poly(ethylene imine) (PEI) to transfer a pattern of amide-coupled PEI, where the pendant, unreacted amines of PEI can be used for subsequent nucleophilic reactions. This procedure can introduce patterned biotin... 

Sulfonylureas are not directly amenable to gas chromatography (GC) because of their extremely low volatility and thermal instability. GC has been used in conjunction with diazomethane derivatization, pentafluorobenzyl bromide derivatization, and hydrolysis followed by analysis of the aryl sulfonamides. These approaches have not become widely accepted, owing to poor performance for the entire family of sulfonylureas. Capillary electrophoresis (CE) has been evaluated for water analysis and soil analysis. The low injection volumes required in CE may not yield the required sensitivity for certain applications. Enzyme immunoassay has been reported for chlorsulfuron and triasulfuron, with a limit of detection (LOD) ranging from 20 to 100 ng kg (ppt) in soil and water. 

In 1994, only 15% of EPA method validations (tolerance method validation and environmental chemistry method validations) that involved GC were carried out using GC/MS. In 2002, this number is reversed in that 85% of the GC methods that were validated by both programs used GC/MS. Many of the compounds investigated in these method trials were polar compounds, and hence these compounds required derivatization in order to be amenable to GC. One common methylating agent is (trimethylsilyl)diazomethane, which is used, for example, to methylate the sulfonamide flumetsulam. As opposed to HPLC/MS, where derivatization is often not necessary, the GC/MS procedure involves an extra step to methylate this compound, under dry conditions, prior to determination by GC/MS. 

Not all drugs contain functional groups that lend themselves readily to prodrug derivatization. A case in point is the carbonic anhydrase inhibitors such as acetazolamide, ethoxzolamide, and methazolamide. Although the amino functional group of their sulfonamide moiety can be methylated, the resulting analogs... 

Amino acid duplications, in sulfonamide resistance, 23 505 Amino acid inhibitors, 13 300-302 Amino acid racemization dating, 5 752 Amino acid residues, 9 494 26 376 Amino acids, 2 554-618 20 447 achiral derivatizing agents, 6 96t analysis, 2 596-600 analysis in green coffee, 7 253t analysis in roasted, brewed, and instant coffee, 7 255t... 

The combinatorial reactions chosen for the novel amines were amide bond formation and sulfonamide formation. The novel carboxylic acids were derivatized to simple amides. For the amine reactions, we chose two simple carboxylic acids (propionic acid and benzoic acid) and two simple sulfonyl chlorides (methyl-sulfonyl chloride and benzenesulfonyl chloride) as the capping groups. Propyl amine and benzylamine were chosen as the capping groups to react with the novel carboxylic acids. Because only one reactant will be variable, these combinatorial libraries were essentially 1 x N libraries, where the one reactant was a simple reactant and the N component is the novel amines or acids. 

Gas chromatographic separation has not gained wide acceptance in spite of being quite sensitive and specific. This mode of separation is complicated by the need for derivatization of sulfonamide residues before gas chromatographic analysis. These drugs are subjected to derivatization via methylation with diazomethane (223, 224, 253, 254, 271), or double derivatization via methylation followed either by silylation with Ai-methyl-Ai-trimethylsilytrifluoroacetamide (261) or by acylation with A-methyl-bis(trifluoroacetamide) (256). This derivatization step is required not only to form the volatile derivatives of the sulfonamides but also to improve their chromatographic properties (thermal stability and decreased polarity). 

Fluorometric detection has also been employed for the determination of sulfonamides in edible animal products, because it confers the advantages of selectivity and sensitivity. Although sulfonamides possess weak native fluorescence, their sensitive lluorometric detection necessitates use of precolumn or postcolumn derivatization producing the corresponding fluorescent derivatives. The most commonly used derivatizing reagent for precolumn derivatization is fluorescamine (217, 228, 230, 238, 239), while for postcolumn derivatization fluorescamine (231), and o-phthalaldehyde (OPA), and -mercaptoethanol (219) are most often used. 

The great variety of incorporable building blocks also offers the synthetic chemist many potential structural and functional design possibilities. The insertion of, e.g., photo-responsive elements, groups with further supramolecular derivatization potential, or sulfonamide units which enable subsequent inter- and intramolecular linkage of catenanes and rotaxanes might render good service in the development of molecular switches [64] and devices [65]. 

P Vinas, CL Erroz, N Campillo, M Hernandez Cordoba. Detennination of sulfonamides in foods by liquid chromatography with post-column fluorescence derivatization. J Chromatogr A 726 125 -131, 1996. 

Font, H., J. Adrian, R. Galve, et al. 2008. Immunochemical assays for direct sulfonamide antibiotic detection in milk and hair samples using antibody derivatized magnetic nanoparticles. J. Agric. Food Chem. 56 736-743. 

Many derivatization techniques, based on chemical reactions or even heat and chemical reactions, can be applied to TLC or HPTLC to specifically determine some compounds or groups of compounds this is specific to TLC techniques. For instance, exposure to fluorescamine in acetone wiU convert sulfonamide antibiotics into fluorescent derivatives which can be visualized under UV radiation [8]. Other techniques are reported and, as suggested earher, the reader should refer to the latest edition of the Official Methods of Analysis pubhshed by the Association of Official Analytical Chemists (Arlington VA, U.S.A.) for complete details about aU the available techniques for the routine analysis of drugs. 

A novel route for the synthesis of piperazin-2-ones on a solid support relies on an intramolecular Mitsunobu reaction [111]. First, commercially available amino alcohols are attached to an aldehyde resin by reductive ami-nation. The alcohol function is protected and the secondary amine obtained is acylated with an amino add. Sulfonamide activation of the free amino group allows intramolecular alkylation through a Mitsunobu reaction, and thereby the formation of a derivatized ring. 

Carbonic Acid Derivatives on Resin Carbamate derivatization of some common hydroxy resins (i.e. hydroxymethylpolystyrene, Wang or the oxime resins) has also been described for the synthesis of ureas, sulfonamides and dihydropyri-... 

Figure 15.3 Urea and sulfonamide synthesis from carbamate derivatized oxime (19), thiophenol (16) and Wang (4) resins.

Tsai, C.-E. Kondo, F. A sensitive high-performance liquid chromatographic method for detecting sulfonamide residues in swine serum and tissues after fluorescamine derivatization. J.Liq.Chromatogr,... 

FIGURE 9.10 Derivatization of TMA and DMA. DMA and TMA were derivatized to form A,A-dimethyl-p-toluene sulfonamide and Af,A-dimethyl-2,2,2-trichloroethyl carbamate. These were isolated using gas chromatography and fragmented using electron impact ionization. 

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