Hydantoin ring opening

Belafdal, 0., M. Bergon, and J.P. Calmon. Mechanism of hydantoin ring opening in iprodione in aqueous media, Pestic. Sci.,... 

Addition of a radical to the C6-position of thymine residues in DNA generates the C5-thymine radical 74 (Scheme 8.27). Reaction with molecular oxygen, followed by reduction, yields the hydroperoxide 75. Decomposition of the hydroperoxide ultimately yields the hydantoin nucleobase 78 via the ring-opened derivatives 76 and 77 ti,2 for the decomposition of 75 in aqueous solution is slow, with a 9 h for the tra i-isomer and 20 h for the c -isomer of the nucleoside)... 

V-Subslilulion and 5,5-disubstitution prevent ring opening as demonstrated by various examples. Ethotoin (3-ethyl-5-phenylhydantoin, 4.230), in contrast to its /V-dcclhylalcd metabolite, was not detectably hydrolyzed by DHPase. No ring-opened metabolite was found for phenytoin (5,5-diphenyl-hydantoin, 4.231) or nirvanol (5-ethyl-5-phenylhydantoin, 4.232), which is the AT-demethylated metabolite of mephenytoin (4.233) [144],... 

Resistance to reduction processes seems to be a general characteristic as most catalytic methods (as well as sodium in ethanol) reduce only the ring. However hydantoin can be reduced by diisobutylaluminum hydride to imidazolin-2-one (81TL2063), and imidazoline-2-thiones can be prepared from 2-thiohydantoins (70AHC(12)103). Oxidative procedures often result in ring opening (B-76MI4070i). 

Dihydropyrimidinase, an enzyme responsible for the hydrolytic ring opening reactions of dihydrothymine (16) and dihydrouracil (17), was partially purified and characterized from calf and rat liver. The enzyme from both sources catalyzed the hydrolytic ring-opening of dihydrouracil, hydantoin (18), 5-phenylhydantoin (19), and a-phenylsuccinimide (20). 

A different means of opening the hydantoin ring is presented by the molecule F (JCj = 0.016 mM) [105] (for molecular structure see Fig. 14). Though there has not yet been a synthetic counterpart of F in the N-acyl-glycosylamie series, a comparison with molecule A (from Fig. 13 (Ki -... 

Moreover, the isocyanate photoproduct was found to undergo hydrolysis at both the isocyanate and adjacent carbonyl groups, producing urea and amide derivatives, respectively.381 The exact position of ring opening at the C-4—C-5 bond was evidenced by the formation of 137 during photolysis of 136 (R = Et, Ph) but the formation of hydantoin derivative 138 by an elimination... 

Barbiturates, hydantoins, and imides contain functional groups related to amides but tend to be more reactive. Barbituric acids such as barbital, phenobarbital, amobarbital, and metharbital undergo ring-opening hydrolysis, as shown in Scheme 15.80-81 Decomposition products formed from these drug substances are susceptible to further decomposition reactions such as decarboxylation. The hydrolysis rates of these substances depend on the substituents Ri, R2, and R3. For some allylbarbituric acids, the effects of these substituents on hydrolysis rates can be explained in terms of Hammett s o value.82... 

Seven-membered meso-cyclic sulfate 291 also undergoes ring opening with sodium diethylphosphite in DMF to give diethylphosphono alcohol 292, which after hydrolysis (95TA3055) is finally converted into optically active hydantoins 293 (Scheme 74). 

D-hydantoinase (EC 3.5.2.2) has been identified as one of the main biocatalysts currently on the market in the fine chemicals industry. The market estimate for using the hydantoinase to produce D-p-hydroxyphenylglycine was US 2 million in 1988. D-hydantoinase (EC 3.5.2.2) is a cyclic amide amidohydrolase opening stereoselectively carbon-nitrogen bonds of cyclic amides such as the dihydropyrimidine and hydantoin rings and 5 -monosubstituted hydantoins. The latter are hydrolysed by D-hydantoinase into N-carbamyl D-amino acids which can be converted chemically or enzymically (N-carbamyl-amidohydrolase, EC 3.5.1.6) to optically active amino acids (Figure 1). 

Benzoxazolone ring opening l-(o-Hydroxyaryl)hydantoin ring... 

As described in the Introduction, spontaneous racemization under alkaline condition is a typical feature of hydantoin. The rate of spontaneous racemization is very much influenced by the electronic properties of the C-5 substituent. Substituents with electronegative inductive effect will stabilize the enolate structure because electron density at C-5 is lowered, thus favoring the release of the proton at C-5. Therefore, hydantoins carrying a carboxy group on an alkyl side chain such as 5-(2 -carboxyethyl)hydantoin, and those carrying arylalkylated or aryl side chain, will readily racemize often within minutes. On the other hand, it may take hours to racemize merely alkylated hydantoins. Hydantoins are more or less unstable in the presence of alkali, and the equilibrium shifts to the direction of ring opening hydrolysis. 

There is no reason to believe that the N ion (or the corresponding ion-pair) derived from NCA (or hydantoin) is an exceptional base, more efficient in attacking an NCA molecule and opening its ring than any other sufficiently basic ion1 (or its ion-pair). Hence, the reactions such as... 

A novel reaction of pyroglutamate (6) and an isocyanate promoted by NaH in THF leads to functionalized hydantoins (7) in good yields. The reaction involves the ring closure of intermediate (8) by a nucleophilic attack on the carbonyl of the ester function followed by expulsion of an alkoxide anion resulting in the formation of the bicyclic intermediate (9). The alkoxide anion in turn can open this bicyclic intermediate with formation of anions (10) and (11) leading to the final racemic hydantoins (7) (Scheme 3).8... 

From both a biochemical and a synthetical point of view the synthesis of hydrogenated uracils by direct reduction of the pyrimidine ring is a reaction of considerable importance. These reduced uracils bear a similar relationship to /3-aminoacids as the hydantoins do to a-aminoacids. A practical method of reducing uracil combinations, therefore, opens up a new method of synthesizing representatives of this important class of... 

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