Reaction iodoacetate

Methylene iodide [75-11-6], CH2I2, also known as diio dome thane, mol wt 267.87, 94.76% I, mp 6.0°C, and bp 181°C, is a very heavy colorless Hquid. It has a density of 3.325 g/mL at 20°C and a refractive index of 1.7538 at 4°C. It darkens in contact with air, moisture, and light. Its solubiHty in water is 1.42 g/100 g H2O at 20°C it is soluble in alcohol, chloroform, ben2ene, and ether. Methylene iodide is prepared by reaction of sodium arsenite and iodoform with sodium hydroxide reaction of iodine, sodium ethoxide, and hydroiodic acid on iodoform the oxidation of iodoacetic acid with potassium persulfate and by reaction of potassium iodide and methylene chloride (124,125). Diiodoform is used for determining the density and refractive index of minerals. It is also used as a starting material in the manufacture of x-ray contrast media and other synthetic pharmaceuticals (qv). 

How might iodoacetic acid affect the glyceraldehyde-3-phosphate dehydrogenase reaction in glycolysis Justify your answer. 

The different configurations of the salts obtained by var3dng the sequence of alkylation are well illustrated by the reaction of pseudo-tropine (14) with ethyl iodoacetate to give 15, while the opposite order... 

Problem 26.10 1 Show the structure of the product you would expect to obtain by SN2 reaction of a cysteine residue with iodoacetic acid. 

Asymmetric additions of Reformatsky-type reagents to nitrones 258a and 258b have also been reported (Scheme 139). The reagents were prepared in situ from ZnEt2 and the corresponding iodoacetic acid ester. Diisopropyl (R,R)-tartrate 262 was employed as a chiral inductor. Enantioselectivities varied significantly the best results were obtained at 0 °C when a nitrone was added to the reaction mixture over a 2 h period. 

Add iodoacetate to a concentration of 50mM in the reaction solution. Alternatively, add a quantity of iodoacetate representing a 10-fold molar excess relative to the number of —SH groups present. An estimation of the sulfhydryl content in the protein to be modified can be accomplished by performing an Ellman s assay (Chapter 1, Section 4.1). Readjust the pH if necessary. To aid in adding a small quantity of iodoacetic acid to the reaction, a concentrated stock solution may be made in the reaction buffer, the pH re-adjusted, and an aliquot added to the protein solution to give the desired concentration. 

Figure 22.30 An iodoacetamide derivative of PE containing an extended spacer arm can be constructed through a carbodiimide coupling of iodoacetic acid to PE, followed by reaction with 2-mercaptoethylamine, and finally another reaction with iodoacetate.

Figure 25.18 An amine-derivative of dextran may be coupled with iodoacetic acid using a carbodiimide reaction to produce a sulfhydryl-reactive iodoacetamide polymer.

Analyses of enzyme reaction rates continued to support the formulations of Henri and Michaelis-Menten and the idea of an enzyme-substrate complex, although the kinetics would still be consistent with adsorption catalysis. Direct evidence for the participation of the enzyme in the catalyzed reaction came from a number of approaches. From the 1930s analysis of the mode of inhibition of thiol enzymes—especially glyceraldehyde-phosphate dehydrogenase—by iodoacetate and heavy metals established that cysteinyl groups within the enzyme were essential for its catalytic function. The mechanism by which the SH group participated in the reaction was finally shown when sufficient quantities of purified G-3-PDH became available (Chapter 4). 

A novel aromatic substitution reaction with electron-deficient radicals, which avoids the use of stannanes, is promoted by the addition of tetra-n-butylammonium bromide [54]. Iodoacetonitrile and iodoacetic esters react with pyrroles and indoles in good to high yield upon photolysis in the presence of 2-methyloxirane and sodium thiosulphate (Scheme 6.34). 

AMDase requires no coenzymes, such as biotin, coenzyme A, and ATP this reaction is inhibited by thiol specific reagents, such as PCMB and iodoacetate... 

The synthesis of oxygen heterocycles in which cyclization onto a pendant alkyne is a key step has also been achieved. Reaction (7.36) shows an example of iodoacetal 29 cyclization at low temperature that afforded the expected furanic derivative in moderate Z selectivity [47]. A nice example of Lewis acid complexation which assists the radical cyclization is given by aluminium tris(2,6-diphenyl phenoxide) (ATPH) [48]. The (3-iodoether 30 can be com-plexed by 2 equiv of ATPH, which has a very important template effect, facilitating the subsequent radical intramolecular addition and orienting the (TMS)3SiH approach from one face. The result is the formation of cyclization products with Z selectivity and in quantitative yield (Reaction 7.37). 

Recently, Duirk et al. [34] showed evidence that iodinated X-ray contrast media (ICM), such as iopamidol, constitute an iodine source to form iodo-THM DBFs, e.g., dichloroiodomethane, and iodo-acid DBFs, e.g., iodoacetic acid, in chlorinated and chloraminated drinking waters. However, the complete reaction pathway is not fully understood yet, and it is under further investigation. Chloraminated and chlorinated source waters with iopamidol were genotoxic and cytotoxic in mammalian cells. This is in agreement with the previously reported high genotoxicity and cytotoxicity of the iodo-acids and iodo-THMs [20, 21]. 

More recently, Kim and coworkers have developed a novel radical alkylation reaction of organic nitro derivatives 16a-d via bis(silyloxy)enamines 17a-d (Scheme 16). This method enables not only P -alkylation to the nitro gronp, bnt also the conversion of the nitro group (16a-d) into an oxime ether fnnctionahty (18a-d). The irradiation of a solntion of 16a-d with iodomethyl phenyl snlfone (or ethyl iodoacetate) and hexamethylditin in benzene at 300 nm give the oxime ethers 18a-d in good yields. 

Tin-based reagents are not always snitable owing to the toxicity of organotin derivatives and the difficulties often encountered in removing tin residues from the final product. Therefore, the same authors have carried out additional experiments with 17d and several different alkyl halides under tin-free conditions. The treatment of 16d with tert-butyldiphenylsilyl chloride (TBDPSCl) and triethylamine in the presence of silver triflate in CH2CI2 affords the bis(silyloxy)enamine 17d in 92% yield (Scheme 17). When the radical reaction was carried out with ethyl iodoacetate in the presence of 2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as the initiator in CH2CI2, the oxime ether 19 was obtained in 83% yield (Scheme 17). 

In an extension of atom-transfer radical reactions to heterocyclic systems, Byers has introduced a novel methodology for the addition of electron-deficient radicals to unprotected pyrroles and indoles in a stannane-fi ee, non-oxidative process <99TL2677>. For exanqrle, photochemical reaction of pyrrole (33) with etl l iodoacetate (34) in presence of thiosulfiite as an iodine reductant, phase transfer catalyst and propylene oxide led to high yields of the 2-alkylated pyrrole 35 <99TL2677>. 

The iminium ions produced by the C- alkylation of A2-piperideines can have synthetic utility for the formation of additional carbon-carbon bonds. This concept is illustrated (Scheme 12) by the synthesis of vincamone and its epimer from piperideine (120). Treatment of enamine (120) with ethyl iodoacetate gave iminium ion (121) which cyclized to (122) under the reaction conditions. Completion of the synthesis was accomplished by base followed by acid treatment (82TL177). 

Haloacetyl Method The haloacetyl method uses supports that contain lodoacetyl or bromoacetyl groups for the immobilization of ligands through sulfhydryl residues. These supports are usually prepared via the reaction of an amine-containing material with iodoacetic or bromoacetic acid in the presence of ethyldimethylaminopropyl carbodii-mide (EDC) at pH 4 to 5. EDC reacts with the carboxylic acid in iodo- or bromoacetic acid... 

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