Deamination mechanism

Scheme 1 Proposed deamination mechanism of gemcitabine in acidic aqueous solution.

Dahlia tubers, inulin from, II, 254 Dambonitol, III, 46 Damson gum, I, 343 IV, 246, 247 structure of, IV, 253 blood group activity of, IV, 50, 52 Deamination, mechanism of, II, 62 Degradation, of acylated nitriles of al-donic acids, IV, 119-151 of aldonic acids, III, 149 of aldose sugars, I, 254 enzymatic, of starch and glycogen, III, 251-310... 

See, however, the results of Hovinen and Fishbein (1992, also Hovinen et al., 1992) on the deamination mechanism of methylamine (see Sect. 7.2) and the kinetic investigations made at the University of Santiago de Compostela (Spain) in this Section (Casado et al., 1981 a-1985b). 

Deamination Mechanisms of Open-Chain Amines Substitution Products... 

Woodcock, 1968 Collins, 1971 Moss, 1971, 1974 Kirmse, 1976, 1979 Whittaker, 1978, p. 617), but surprisingly only rarely later (briefly by Laali and Olah, 1985, more extensively by Manuilov and Barkhash, 1990). March reviews extensively other aliphatic nucleophilic substitutions in his book Advanced Organic Chemistry (1992), but he makes little reference to deamination mechanisms. 

The reader who is not well acquainted with the extensive and controversial literature of deamination mechanisms of the last five decades may have the impression from our relatively detailed review of White et al. s recent paper and of the related work of Collins group that the dominant role of ion pairing in deaminations was not clearly recognized earlier. This is by no means the case. The paper of White s group (1992b) was chosen for this discussion because it combines and expands previous partial results with 1-phenylethylamine derivatives for which mechanistic conclusions are not disguised by a multitude of products as they are illustrated in the introductory Scheme 7-1. 

We start this section with a short discussion of conformational control, because conformations of alkylamines and alkanediazonium ions are important factors for the deamination mechanisms. The distribution and configuration of products is often a function of the relative population of conformers. If two conformers yield two different products basically two cases have to be distinguished ... 

In Sections 7.3-7.5, we discussed a selection of investigations on the deamination mechanisms of aliphatic amines by direct nitrosation in various solvents and by rearrangement processes of amine derivatives. These investigations are a very small fraction of all studies made in that area. It would take too many pages to summarize, and even more, to critically discuss the majority of all results. 

In 1983, Kirmse and Siegfried published a paper with the title 2-Norbornane-diazonium Ions Revisited . These authors considered it essential to reinvestigate the deamination of the endo- and exo-norbornylamine, not least within the context of the well-known discussion on nonclassical carbocations. We adopt the word revisit from this paper for this section and combine it with challenge , i. e., an expression indicating encouragement to reinvestigate deamination mechanisms in the future, because today (1995) we still have the impression that there are too many ambiguities in mechanistic interpretations of experimental results in deamination studies. 

As an outsider in the chemistry of bicyclic aliphatic hydrocarbons, I have the feeling that these reactions are intrinsically so complex that it is too difficult to deduce from them generally applicable rules for deamination mechanisms. It would appear that concentration on reagents as simple in structure as possible would be more promising, as purity determinations by instrumental analyses of all types are easier to interpret and as the number of products would be smaller. This is clearly indicated by some of the reactions discussed in Section 7.3, particularly Brosch and Kirmse s stereochemical investigation (1991) of the [l- H]butylamine deamination and the reactions investigated by Fishbein s group, namely the first steps of the methylamine nitrosation (Hovinen and Fishbein, 1992 Hovinen et al., 1992), the decomposition... 

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... 

Petersen-Mahrt, S. K., Harris, R. S., and Neuberger, M. S. (2002). AID mutates . coli suggesting a DNA deamination mechanism for andbody diversification. Nature 99-103. 

Other products that form from the pyrolysis of amino acids are aldehydes, which contain one less carbon atom than the parent amino acid. This process occurs via an SNi deamination mechanism. Another process that can occur is side chain stripping involving chain homolysis. The result is the production of various saturated and unsaturated compounds. Many alpha-amino acids, when pyrolyzed, form an amine fragment, a nitrile fragment, and aldehydes that contain one less carbon atom than the parent amino acid. Also, a side stripping mechanism can result in various saturated and unsaturated compounds. ... 

The usual deamination mechanism is considered to be energetically unfavourable for these substrates, as it would generate a positive centre adjacent to the positive end of the carbonyl dipole, and rearrangement synchronous with nitrogen loss from the diazonium ion is suggested, to allow incipient charge on to be delocalised. A detailed product study of 19 delineates three types of bond rearrangement (reaction 20) . The cyclopentane carboxylic acid may also be... 

LXXX. Nucleophilic addition of an acetate anion gives diacetyl-pseudodiosgenin (LXXXII) and 3j3,25-diacetoxyfurosta-5,20(22)-diene (LXXXIII). In the aqueous medium applied by Sato et al. (246) there may occur the same deamination mechanism, except that under these conditions the nucleophilic addition of water leads to the deacet-ylated derivatives of LXXXII and LXXXIII which are able to recyclize to the spiroketals diosgenin (LXXIV) and the 22,25-epoxyfurostene LXXVI, respectively. This mechanism, which involves the intermediate elimination of the chirality center 22, permits no conclusions with regard to the possible identity of the spirosolane side chain stereochemistry with that of the corresponding spirostanes. 

FIGURE 141.1 (a) The tautomer bypass and the deamination mechanism of CC-dimer mutagenicity, used to explain C —> T transitions and CC —> TT tandem transition mutations, (b) A cytidylyl-cytidine sequence and a situation in which both cytidins are present in their E-imino tautomeric forms. 

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