Hydantoin ring 1- - from

A new N-halamine monomeric compound, hydantoin acrylamide (HA), was synthesised by forming a hydantoin ring from the ketone moiety of a secondary amide monomer, N-(l,l-dimethyl-3-oxobutyl)acrylamide (DA), which has been used for coatings and textile applications [76]. Amide and imide moieties of the hydantoin ring halogenate more easily than sterically hindered secondary amides this method can be used to impart antimicrobial properties to films, coatings or paint. HA can be copolymerised with many commercial monomers. 

Mass spectral fragmentation patterns of alkyl and phenyl hydantoins have been investigated by means of labeling techniques (28—30), and similar studies have also been carried out for thiohydantoins (31,32). In all cases, breakdown of the hydantoin ring occurs by a-ftssion at C-4 with concomitant loss of carbon monoxide and an isocyanate molecule. In the case of aryl derivatives, the ease of formation of Ar—NCO is related to the electronic properties of the aryl ring substituents (33). Mass spectrometry has been used for identification of the phenylthiohydantoin derivatives formed from amino acids during peptide sequence determination by the Edman method (34). 

One of the most widely used enzymatic methods for D-amino acid production is the hydantoinase process [4]. The great advantage of this process is that, potentially, any optically pure D-amino acid can be obtained using the corresponding substrate from a wide spectrum of D,L-5-monosubstituted hydantoins, which are readily accessible by chemical synthesis [5]. In this cascade of reachons the chemically synthesized D,L-5-monosubstituted hydantoin ring is first hydrolyzed by a stereoselective hydantoinase enzyme (D-hydantoinase). Further hydrolysis of the resulting N-carbamoyl D-amino acid to the free D-amino acid is catalyzed... 

Monosubshtuted hydantoins are a-amino acids cyclically protected at both the carboxyl- and the a-amino group. They can be easily prepared from an aldehyde and isocyanate or by the Bucherer-Bergs synthesis and similar methods. Indeed, the hydantoin synthesis is also a prachcal method for the preparahon of the racemic amino acid. Enzymes belonging to the dihydro-pyrimidinase family hydrolyze hydantoins to the carbamoyl amino acid. The latter can be hydrolyzed in turn to the amino acid by a second enzyme, a carbamoylase. Both enzymes can discriminate between enantiomers and, if their action is cooperative, either the L- or the D-amino acid can be obtained (Scheme 13.10) [36]. What makes the system of special interest is that the proton in the 5-position of the hydantoin ring (it will become the a-hydrogen in the a-amino acid) is considerably more acidic than conventional protons in amino acid esters or amides and much more acidic than the amino acid itself. Thus, the hydantoin can be often racemized in situ at slightly basic pH where the enzymes are stiU stable and active. If these condihons are met. 

Note that the highest IDT was obtained with the cyclopenta-methylenehydantoin resin derived from cyclohexanone. It is tempting to speculate that this inflexible alkylene moiety was ineffective in shielding the hydantoin ring, but subsequent comparison of the hydrophobic-hydrophilic balance of amine-cured resins appeared to rule out this explanation probably the stiff spiro structure contributed to the high Tg, just as it contributed to the high melting point of the resin itself (lie). 

The hydrophobic shielding of the hydantoin ring by alkyl substituents affected all the solvent-solute interactions of cured resins. Two of the resins and the DMH-based resin mixture were cured with a commercially available aromatic amine mixture derived from aniline-formaldehyde condensation, identified in Table VII. Weight gain and solvent plasticization were followed in a number of solvents and aqueous media. Some of the exposure was at 60 C as well as at room temperature. 

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 -... 

Amino acids have also been obtained by acid hydrolysis of hydantoins and 2-thiohydantoins under relatively drastic conditions.1,3 4-Thiohydantoin is hydrolyzed with hot concentrated hydrochloric acid to hydantoin, and boiling 20% aqueous chloroacetic acid completely removes sulfur from 2,4-dithiohy-dantoin to form hydantoin derivatives. (Scheme 8). These reactions reflect the intrinsic stability of the hydantoin ring. 

A typical way to synthesize a hydantoin core starting from a resin-bound amino acid is shown in Scheme 9.10. Fmoc-amino acid loaded polystyrene resin 77 was deprotected in 20% piperidine in NMP, which then underwent a reductive alkylation process in an NMP solution of 6 equiv of isocyanate (78) and 1 equiv of DIEA for 3 h, affording the urea derivatives 79. Cyclocleavage of 79 was carried out in 10% triethylamine in methanol, shaking for 3h, to give the desired hydantoin ring 80. 

Cyclization is known to release resin-bound compounds without a linker. Hydantoin ring formation releases resin-bound compounds smoothly, producing interesting hydantoin derivatives with potential medicinal or biological activity. Resin-bound alkenes reacted with nitrile oxides that were generated with Mukaiyama s method from nitroalkane (Scheme 11.48). The isoxazolines were cleaved from the resin via ahydantoin formation upon heating under basic conditions. 

The key structural feature of BIRT-377 (1) is the A-aryl-substituted-hydantoin bearing a quaternary stereogenic center. In our retrosynthetic analysis, the hydantoin ring can be synthesized by cyclization of the corresponding acyclic a-substituted amino acid amide (9), which could be derived from (Z>) or (L)-alanine. 

The two groups of enzymes discussed here have attracted attention because both offer a useful broad spectrum of substrate specificity. They are grouped together because in the context of amino acid synthesis they form a natural pair. Amino acid hydantoins are convenient from the standpoint of organic synthesis. The hydantoinases cleave the ring, producing the A-carbamoyl derivative of the amino acid. This must then be further hydrolyzed to obtain the free amino acid, and this step is likely to be strictly enantioselective (Equation (10)). 

A somewhat different scheme is used for the preparation of an all-aliphatic thio-hydantoin. Thus, reaction of racemic leucine (91-1) with allylisothiocyanate (91-2) leads to the thiourea (91-3). Attack of the anion from treatment of that intermediate with a strong base leads to ring closure and the formation of the imidazoline ring. There is thus obtained the anticonvulsant agent albutoin (91-4) [97]. 

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... 

To increase the number of diversities, the hydantoin (or thiohydantoin) formation reaction was performed starting from N-alkylated dipeptides (Fig. 3). In the last synthesis step, the hydantoin (or thiohydantoin) ring was alkylated followed by the cleavage from the resin. Using 54 different amino acids for the first position of diversity (R1), 60 different amino acids for the second position of diversity (R2), and four different alkylating... 

Fluorous aminoesters have also been used in DOS of three unique triaza tricyclic and tetracyclic ring systems (Scheme 22) [44], Bicyclic pyrrolidines 12 generated from one-pot, three-component 1,3-dipolar cycloaddition of azomethine ylides were further converted to hydantoin-, piperazinedione-, and benzodiazepine-fused compounds 31-33, respectively. Each of these three heterocyclic scaffolds has four stereocenters on the central pyrrolidine ring and up to four points of diversity (R1 to R4). The structure of compound... 

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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