Biological nucleophiles

The reactive electrophilic acyl and carbonyl compounds produced by oxidative dehalogenation may react with nucleophilic biological molecules such as DNA, proteins, lipids and carbohydrates to possibly form toxic metabolites. 

Many 2-substituted 5-nitrothiazoles are prepared (by nucleophilic substitution reactions on 2-halogeno-5-nitrothiazoles) for use as biocides or for their biological activity (31, 91-95). 

Nucleophilic substitution is one of a variety of mechanisms by which living systems detoxify halogenated organic compounds introduced into the environment Enzymes that catalyze these reactions are known as haloalkane dehalogenases The hydrolysis of 1 2 dichloroethane to 2 chloroethanol for example is a biological nude ophilic substitution catalyzed by a dehalogenase... 

The reactivity of epoxides toward nucleophilic ring opening is responsible for one of the biological roles they play Squalene 2 3 epoxide for example is the biological... 

A naturally occurring sulfonium salt S adenosylmethionme (SAM) is a key sub stance in certain biological processes It is formed by a nucleophilic substitution m which the sulfur atom of methionine attacks the primary carbon of adenosine triphosphate dis placing the triphosphate leaving group as shown m Figure 16 7... 

The next section explores the mechanism of nucleophilic addition to aldehydes and ketones There we 11 discuss their hydration a reaction m which water adds to the C=0 group After we use this reaction to develop some general principles we 11 then survey a number of related reactions of synthetic mechanistic or biological interest... 

Amines like ammonia are weak bases They are however the strongest uncharged bases found m significant quantities under physiological conditions Amines are usually the bases involved m biological acid-base reactions they are often the nucleophiles m biological nucleophilic substitutions... 

An imidazole ring is a structural unit m the ammo acid histidine (Section 27 1) and is involved m a large number of biological processes as a base and as a nucleophile... 

The quiaones have excellent redox properties and are thus important oxidants ia laboratory and biological synthons. The presence of an extensive array of conjugated systems, especially the a,P-unsaturated ketone arrangement, allows the quiaones to participate ia a variety of reactioas. Characteristics of quiaoae reactioas iaclude nucleophilic substitutioa electrophilic, radical, and cycloaddition reactions photochemistry and normal and unusual carbonyl chemistry. 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Such calculations have been made also for pyrimidines of biological interest (B-60MI21302). That for uracil (5) is interesting in that a figure of -0.22 is assigned to the 5-position, compared with almost zero in pyrimidine this immediately explains the ease of electrophilic attack at the 5-position of uracil as well as the lack of nucleophilic activity at the same position. 

Pyrido[2,3-d]pyridazine, 1 -chloro-4-hydrazino-biological activity, 3, 261 Pyrido[2,3-(i]pyridazine, 4-chloro-l-hydrazino-biological activity, 3, 261 Pyrido[2,3-(i]pyridazine, 5,8-dichloro-nucleophilic substitution, 3, 242 Pyrido[2,3-(i]pyridazine, polyhalo- H NMR, 3, 234... 

Pyrido[3,4-d]pyrimidine-2,4-dione synthesis, 3, 215 Pyridopyrimidines, 3, 201 iV-alkylations, 3, 206 biological activity, 3, 260-261 1-electron reductions, 3, 207 IR spectra, 3, 204 mass spectra, 3, 204 MO calculations, 3, 204 NMR, 3, 202, 203 nucleophilic substitution, 3, 213 8-nucleosides synthesis, 3, 206 physical properties, 3, 201-205 protonation, 3, 206 radical reactions, 3, 215 reactions with water, 3, 207 reduced... 

Dmitrofluorobenzene also serves as an arylation agent for a wide vanety of biologically useful amines including aromatic amines [5b], ammo acids [57], and ammocarbohydrates [55,59] Weak nucleophilic amines such as benzimidazole [60] and fluoroamines [61] can also be arylated (equation 30)... 

Of all known [4+1] cycloadducts, the ttn heterocycles exhtbit the most interesting preparative potential [I33 On heating they are transformed into 5-fluoro-4-tnfluoromethyl-l,3 azoles [132, 133] The fluorine atom at C-5 can be replaced by various nucleophiles By this route, the 4-trifluoromethyl-l 3-azole moiety can be introduced into many compounds of biological interest (equation 31)... 

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