Hydrolysis of diisopropyl

In curve g all three terms are important, and the range of hydrogen ion concentration where the velocity of the reaction is independent of hydrogen ion and hydroxyl concentration depends on the magnitude of the water reaction relative to and /i oh- and the ratio / h,o to fcoH In the case of the mutarotation of glucose (Brpnsted and Guggenheim, 37) this range is from 10 to 10 , for the hydrolysis of diisopropyl fluophos-phate (Kilpatrick and Kilpatrick, 38), 10 to 10 . ... 

Wagner-Jauregg, T., Hackley Jr., B.E., Lies, T.A., Owens, O.O., and Proper, R. 1955. Model reactions of phosphoms-containing enzyme inactivators. IV. The catal)Tic activity of certain metal salts and chelates in the hydrolysis of diisopropyl fluorophosphate. Journal of the American Chemical Society, 77 922-929. 

Diisopropylurea IV,/V -Diisopropy lurea N, N tns-( 1 -Methylethyl) urea c7h16n2o 4128-37-4 Hydrolysis of diisopropyl carbodiimide... 

Gustafson RL, Chaberek S and Martell AE (1963). A kinetic study of the cipper (n) chelate catalyzed hydrolysis of diisopropyl phosphofluoridate. J Am... 

FIGURE 59.2 (A) Hydrolysis of paraoxon with aryldiaUcylphos-phatase (paraoxonase, EC 3.1.8.1) and (B) hydrolysis of diisopropyl-fluorophosphate (DFP) with diisopropylfluorophosphatase (DFPase) (EC 3.1.82). 

Regioselective hydrolysis of diesters is a challenging problem ia synthetic chemistry because the side reactions always reduce the yield of desired product. Some Upases are well suited to perform this task. Lipase OF-360 (Meito Sangyo) hydrolyzes diester (55) ia 74% theoretical yield and 93% ee (70). Lipase from Pseudomonas cepacia suspended ia diisopropyl ether saturated with water hydrolyzes triester (56) with a remarkable efficiency and regio- and stereoselectivity (71). 

The addition of HCN to aldehydes or ketones produces cyanohydrins. This is an equilibrium reaction. For aldehydes and aliphatic ketones the equilibrium lies to the right therefore the reaction is quite feasible, except with sterically hindered ketones such as diisopropyl ketone. However, ketones ArCOR give poor yields, and the reaction cannot be carried out with ArCOAr since the equilibrium lies too far to the left. With aromatic aldehydes the benzoin condensation (16-54) competes. With oc,p-unsaturated aldehydes and ketones, 1,4 addition competes (15-33). Ketones of low reactivity, such as ArCOR, can be converted to cyanohydrins by treatment with diethylaluminum cyanide (Et2AlCN see OS VI, 307) or, indirectly, with cyanotrimethylsilane (MesSiCN) in the presence of a Lewis acid or base, followed by hydrolysis of the resulting O-trimethylsilyl cyanohydrin (52). The use of chiral additives in this latter reaction leads to cyanohydrins with good asymmetric... 

Ivie 1980) and quantification of its urinary metabolites in various animal species (Bucci et al. 1992 Hart 1976 Ivie 1980 Snodgrass and Metker 1992 Weiss et al. 1994). Hydrolysis of one of the two phosphate ester bonds liberates isopropanol and converts diisopropyl methylphosphonate to IMPA. The locations of the enzymes capable of catalyzing diisopropyl methylphosphonate phosphate ester hydrolysis have not been identified. 

This enzyme [EC 3.4.16.5] (also known as serine-type carboxypeptidase I, cathepsin A, carboxypeptidase Y, and lysosomal protective protein) is a member of the peptidase family SIO and catalyzes the hydrolysis of the peptide bond, with broad specificity, located at the C-terminus of a polypeptide. The pH optimum ranges from 4.5 to 6.0. The enzyme is irreversibly inhibited by diisopropyl fluorophosphate and is sensitive to thiolblocking reagents. 

The mammalian serine proteases have a common tertiary structure as well as a common function. The enzymes are so called because they have a uniquely reactive serine residue that reacts irreversibly with organophosphates such as diisopropyl fluorophosphate. The major pancreatic enzymes—trypsin, chymotrypsin, and elastase—are kinetically very similar, catalyzing the hydrolysis of peptides... 

The preceding experiments prove that there is an intermediate on the reaction pathway in each case, the measured rate constants for the formation and decay of the intermediate are at least as high as the value of kcat for the hydrolysis of the ester in the steady state. They do not, however, prove what the intermediate is. The evidence for covalent modification of Ser-195 of the enzyme stems from the early experiments on the irreversible inhibition of the enzyme by organo-phosphates such as diisopropyl fluorophosphate the inhibited protein was subjected to partial hydrolysis, and the peptide containing the phosphate ester was isolated and shown to be esterified on Ser-195.1516 The ultimate characterization of acylenzymes has come from x-ray diffraction studies of nonspecific acylenzymes at low pH, where they are stable (e.g., indolylacryloyl-chymotrypsin),17 and of specific acylenzymes at subzero temperatures and at low pH.18 When stable solutions of acylenzymes are restored to conditions under which they are unstable, they are found to react at the required rate. These experiments thus prove that the acylenzyme does occur on the reaction pathway. They do not rule out, however, the possibility that there are further intermediates. For example, they do not rule out an initial acylation on His-57 followed by rapid intramolecular transfer. Evidence concerning this and any other hypothetical intermediates must come from additional kinetic experiments and examination of the crystal structure of the enzyme. 

The Amano researchers found not just drastically different enantiomeric excesses in the Pseudomonas sp. (Amano AH) lipase-catalyzed hydrolysis of methylene-oxypropionyl or -pivaloyl diesters, but a near-total reversal of specificity. Whereas in cyclohexane the different esters yielded half-esters with 88.8-91.4% e.e. -specificity for a triple mutant ( FVL ) of Amano PS lipase, the same transformation with the same enzyme in diisopropyl ether (DIPE) yielded between 68.1 and > 99% e.e. of the S-product (Figure 12.10) (Hirose, 1992,1995). 

Hydrolysis of stabilizer N-N -diisopropyl carbodiimide, 17 2-3 Simplified scheme for the hydrolysis of VX, 17 2-4 Major hydrolysis pathways for mustard, 18... 

Lefebvre and Evans found that lithium diethyl phosphite [(EtO)2POLi] adds to (Ss)-N-benzylidene-p-toIuenesulfinamide (126) to give (Ss,S)-128 in 85% yield and 84% de.77 The diastereomeric excess was improved to 93% de by using the sodium salt and to >97% with lithium diisopropyl phosphite. Transition state 127, involving si-face attack of the nucleophile, was proposed to account for the favored formation of 128. a-Aminobenzyl phosphonic acid 129 was obtained on hydrolysis of 128.78 Similar results were reported for the addition of diamido phosphite to 126.78... 

Note, too, the mild conditions used for the formation of the diisopropyl acetal 552 from aldehyde 55,1 again without p-elimination. Another example comes from a synthesis of Arachidonic Add in which a key step was the mild hydrolysis of a diisopropyl acetal under conditions that do not provoke rearrangement of the p,y-double bond into conjugation with the aldehyde function.118 The method has been applied to the synthesis of a number of natural (Z,Z)-skipped 1,4-dienes.119... 

Carbene adducts of a range of sulfur compounds have also been isolated. Carbene (1) (R = i-Pr, R = Me) reacts with sulfur dichloride or thionyl chloride to yield the hyperva-lent sulfur derivatives (118) and (119). Similarly, reaction of carbene (2) (R = r-Bu) with SO2 led to the formation of the 1 1 adduct (2)-SO2 (120). In contrast, reaction of carbene (1) (R = i-Pr, R = Me) with SO2CI2 affords the 2-chloro-l,3-diisopropyl-4,5-dimethylimidazohumchlorosul-fite salt (121). A carbene adduct of SO3 (122) can then be isolated through hydrolysis of (121) in the presence of cyanide. 

Blum, M.M., Timperley, C.M., Williams, G.R., Thiermann, H., Worek, F. (2008). Inhibitory Potency against human acetylcholinesterase and enzymatic hydrolysis of fluorogenic nerve agent mimics by human paraoxonase 1 and squid diisopropyl fluorophosphatase. Biochemistry 47(18) 5216-24. 

Nerve agents are hydrolyzed by the enzyme organophosphate (OP) hydrolase. The hydrolysis of GB, soman (GD), tabun (GA), and diisopropyl flu-orophosphate occurs at approximately the same rate. The isomers of the asymmetric OPs may differ in overall toxicity, rate of aging, rate of cholinesterase inhibition, and rate of detoxification. The rates of detoxification differ for different animal species and routes of administration. The onset of effects from nerve agents depends on the route, duration, and amount of exposure. The effects can occur within seconds to several minutes after exposure. There is no... 

Bluegill and catfish were both able to hydrolyze DFP, dichlorvos, and dimethyl 2,2,2-trichloro-l-n-butyryloxyethyl phosphonate (butonate). Catfish enzymes were also able to hydrolyze paraoxon and methyl 3-hydroxy-alpha-cronate dimethyl phosphate (mevinphos) although at a very slow rate. Kms calculated for the enzymes of both species indicated that each had a greater affinity for DFP than dichorvos. Sulfhydryl reagents and Cu2+ were found to inhibit the enzymatic activity of both organisms. Paraoxon had no effect. Cleavage products were identified as dimethyl phosphate and 2,2-dichloroacetaldehyde from dichlorovos hydrolysis and diisopropyl phosphate from the hydrolysis of DFP. 

Because the exploitation of the chemistry of unprotected phosphonylated acetaldehydes is handicapped by the sensitivity of the P-C bond in acidic media, a reliable alternative procedure for the preparation of dialkyl 1-chloro-1-formylmethylphosphonates from dialkyl 2-ethoxy-vinylphosphonates has been developed. Room-temperatme chlorination of 2-ethoxyvinylphosphonates with dry chlorine in CCI4 followed by hydrolysis of the phosphonylated a,p-dichloro ethers with water at 50-60°C gives the expected monochlorinated aldehydes in 73-82% yields (Scheme 5.70). A similar treatment with bromine in water at 0°C converts diisopropyl 2-ethoxyvinylphosphonate smoothly into diisopropyl 1-bromo-1-formylmethylphosphonate in 92% yield. ... 

Regioselective addition of diisopropyl phosphite to protected derivatives of L-vinylglycine, racemic or enantiomerically pure, in xylene at 120°C catalyzed by tert-butyl per-2-ethylhcxanoatc affords the protected aminocarboxyalkylphosphonate in only moderate yield (3S%, Scheme 8.8S). The L-2-amino-4-phosphonobutanoic acid (APB) is isolated as hydrochlorides by acidic hydrolysis with 6 M HCl. 

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