Deamination elimination mechanisms

Alkylaziridines can be stereospecifically deaminated to alkenes by reaction with m-chioroperbenzoic acid (70AG(E)374). The reaction and work-up are carried out in the dark to avoid isomerization of the cw-alkene, and the mechanism is thought to involve an initial oxidation to an amine oxide followed by a concerted elimination. Aziridine oxides have been generated by treating aziridines with ozone at low temperatures (71JA4082). Two... 

The proposed mechanisms are similar in both cases and involve in particular an (aryl)(hydrido)ruthenium intermediate in which the ruthenium is additionally coordinated by an in. ( ////-generated /V-phenylimine moiety tethered to the same Ru-bound aromatic ring. The C-C bond-forming step for the construction of the corresponding heterocyclic framework proceeds via insertion of the C=N double bond into the C-Ru bond with transfer of the (hydrido) ruthenium complex to the now phenylamine nitrogen. The desired heterocycles 158 and 159 were obtained after successive reductive elimination, deamination, and dehydrogenation. 

The experiments described above indicated amino acids were oxidatively deaminated in liver and their a-amino groups converted to urea. A start on investigations of the mechanism of urea biosynthesis was made by Schultzen and Nenki (1869) who concluded that amino acids gave rise to cyanate which might combine with ammonia from proteins to produce urea. Von Knieren (1873) demonstrated that when he drank an ammonium chloride solution, or gave it to a dog, there was an increase in the formation of urea, without any rise in urinary ammonia. His results were consistent with the cyanate theory but did not eliminate the possibility that urea arose from ammonium carbonate which could be dehydrated to urea ... 

Cytosine can become deaminated spontaneously or by reaction with nitrous acid to form uracil. This leaves an improper base pair (G-U), which is eliminated by a base excision repair mechanism (Figure 1-2-5). Failure to repair the improper base pair can convert a normal G-C pair to an A-T pair. 

The reaction mechanism of amine deamination and disproportionation has been put forward by analogy with other eliminations, namely dehydration and dehydrochlorination [149,155], its characteristic feature being the cooperation of acidic and basic sites. In the deamination, /3-hydrogen and the NR2 group (R is hydrogen or alkyl) are eliminated by an E2-like mechanism on alumina, but by an El-like mechanism on silica-alumina. The nature of the acidic sites is not clear, protons from surface hydroxyls or aluminium ions are possible candidates. However, it seems... 

A fully concerted mechanism for reaction 299 has been eliminated as inconsistent with 14C and 15N KIEs and also with the observed inverse solvent D2O effect. The reaction path for the deamination of AMP has been formulated613 as a stepwise conversion involving the formation of tetrahedral intermediate 515 characterized by full-bonded hydroxyl and amino groups (equation 300). The TS for slow formation of 515, resulting from the attack of the hydroxyl from enzyme zinc-activated water at the C(6), is characterized by the C(6) OH bond order of 0.8 0.1 (late TS) and fully bonded NH2, that is by the nearly complete conversion to sp3 at C(6), and by nearly complete protonation of Nq), 516, The protonation of NH2 (in 515) and departure of NH3 (with TS 517) take place in the subsequent rapid steps as shown in equation 300, Zinc hydroxide is formed prior to attack514 at C(6). Enzymatic degradation of [6-14C]AMP has been carried out to prove the position of the radiolabel in 513 (equation 301). No radioactivity in the allantoin... 

Deamination has also been recognized as the rate-determining step in some replacement reactions carried out on phenolic and indolic Mannich ba-ses. - In phenolic derivatives, in particular (Fig. 88), a pre-equilibrium takes place similar to that described above for p-aminoketones, and is followed by the elimination of amine via an E cB-type mechanism. ... 

Ring closure with concomitant amino group elimination is actually a replacement reaction, as depicted below, strictly connected with the replacement reaction described in Sec. B. Similarly, the cyclization mechanism may or may not involve the formation of a vinyl intermediate (vinylketone, methylcnequinone, etc.), originated by the deamination of the initial Mannich base, which then undergoes addition. 

The mechanism in Figure 16 explains the available information. Initial homolytic dissociation of the Co-C5 bond in coenzyme B12 and abstraction of hydrogen from Cl of HEH by the 5 -deoxyadenosyl radical are thought to be similar to early steps in the catalytic deamination of a substrate by EAL. Elimination of the hydrazine radical cation in the last step in Figure 16 is unlike the normal deamination process in that it involves homolytic cleavage of the C-N bond in HEH. This mode of cleavage appears to occur because of the intrinsic stability of the hydrazine radical cation. 

Fig. 25. A general mechanism of /8 replacement and P elimination-deamination reactions involving a common aminoacrylate intermediate (1).

In common with /8 replacement reactions, /S elimination-deaminations also proceed via the formation of an aminoacrylate species (Fig. 25, 1) protonation of which at Cp followed by hydrolysis leads ultimately to the release of pyruvate and ammonia. However, the exact timing and mechanism of these final steps are at present unclear. 

The drug is eliminated primarily via renal mechanisms as eptifibatide and deaminated eptifibatide. The clinical importance of eptifibatide and its benefits in comparison with other therapeutic agents used in the treatment of acute coronary syndromes and percutaneous coronary intervention have recently been reviewed by Curran and Keating (121). 

The deamination of n-propylamine by nitrous acid and the deoxideation of n-propoxide both give propene and cyclopropane as the elimination products in a ratio of 9 1 (refs. 619, 620). A similar product ratio is obtained from the thermolysis of 1-diazopropane and this raises the possibility that carbenoid intermediates are also involved in the former reactions. However, the products of deoxideation of 1,1-dideuteropropanol are consistent with a carbonium-ion mechanism involving a 1,3-elimination to give the cyclopropane,... 

E. coli cytidine deaminase (CDA) is an enzyme that catalyzes hydrolytic deamination of cytidine to uridine (or from 2 -deoxycytidine to 2 -deoxyuridine) (Scheme 8). This enzyme is considered to be a member of the MMP family, although the Zn -binding site contains two Cys and one His residues. On the basis of the X-ray crystal structure of a transition-state analogue complex,a mechanism was proposed as shown in Scheme 8, in which Glul04 serves multiple roles the deprotonation of the Zn " -bound water and simultaneous protonation to N3 of the substrate (Scheme 8a), stabilization of the first tetrahedral transition state (Scheme 8b), and protonation of the leaving amino group at the 4-position of the substrate in the second tetrahedral intermediate (Scheme 8c).Upon elimination of NH3, an E-P complex is formed (Scheme 8d) and the enzyme goes into the next turnover. The deamination mechanism of E. coli... 

The enzyme serine dehydratase employs pyridoxal phosphate (PEP) in the direct deamination of serine. In this reaction, the a-carbon of serine undergoes a two-electron oxidation through a-elimination. Show how PEP participates in the process by writing a mechanism for serine dehydration and deamination. 

Fig. 4). This reaction is chemically reversible. Oxidation of the G reduction product can be observed in cyclic or in anodic stripping modes if the electrode is shortly exposed to highly negative potentials prior to scanning to positive potentials [136-138]. The mechanism of electroreduction of inosine (nucleoside of hypoxanthine, a deamination product of A) was recently studied using elimination polarography [139]. Reduction of T and U at a mercury electrode can be observed in nonaqueous media [140, 141]. 

Reactions in which a bond from carbon to nitrogen is broken are important in several areas of organic chemistry. The Hofmann and Cope eliminations are widely used in synthetic chemistry, and the deamination of aliphatic amines (via the nitrous acid, nitrosoamide and triazene methods) has been widely studied, usually with a primary emphasis on establishing the mechanism of the reaction. Since there has been much research activity in the latter area recently, a major fraction of the chapter is devoted to an interpretive and critical review of the deamination reactions. 

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