Alkylation reactions biological

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

Michael-type addition of a suitable nucleophile, e.g. thiols, on to the a,f)-unsaturated lactone. Such alkylation reactions are believed to explain biological activity, and, indeed, activity is typically lost if either the double bond or the carbonyl group is chemically reduced. In some structures, additional electrophilic centres offer further scope for alkylation reactions. In parthenolide (Figure 5.31), an electrophilic epoxide group is also present, allowing transannular cyclization and generation of a... 

Carbon-carbon bond formation is a reaction of fundamental importance to the cellular metabolism of all living systems and includes alkylation reactions involving one and five carbon fragments as well as carboxylation reactions. In addition, a very common method of generating carbon-carbon bonds in biology includes the reactions of enolates and their equivalents (such as enamines) with aldehydes, ketones, keto acids, and esters. Reactions in which the enolate derives from an acyl thioester are Claisen condensations, whereas the remainder are classified as aldol reactions. 

The presence of mefhoxy groups in the poly(oxyethyloie phosphate)s predetermines two possible ways for immobilization through an ionic bond of amine-containing biologically active substances (i) alkylation reaction, (ii) dealkylation reaction. Both of them are due to the reactivity of the a-carbon atom of the methoxy group, which acts as an electrophilic center. 

The synthetic utility of DPM-type rearrangements now extends well beyond their application in the synthesis of natural products and biologically active systems. So, for example, dibenzobarrelenes annulated with a pyrrolinium unit (e.g., 142) and including a benzophenone counterion 143 undergo a DPM rearrangement reaction in the solid state, and the product dibenzosemibullvalene 144 serves as a phase-transfer catalyst in alkylation reactions. 

Biological C-alkylation reactions have attracted considerable experimental attention in recent years. As a result of some early studies, in which it was shown that only two of the three hydrogens attached to the methyl carbon are transferred during certain carbon methylations, it appeared that perhaps new chemical or biochemical principles might be involved. Further investigation has shown however, that carbon methylations may rather comfortably be accommodated within the existing theoretical understanding of transmethylation reactions. For these reasons, it may be worthwhile to discuss this area in some detail. 

Many biological macromolecules contain nucleophilic groups that can be alkylated, for instance sulfhydryl, hydroxyl, and amino groups are present in amino acids in proteins, organic bases in DNA, and so on. Therefore, in vivo alkylation reactions are responsible for all kinds of toxic effects from enzyme inhibition to mutagenicity or carcinogenicity. 

It is known that unsaturated groups in heterocyclic compounds increase then-biological activity. For the piupose of direct introduction of allylic and propargyl radicals into the indole ring were studied alkylation reactions by halogenalkyls under condition of interphase catalysis [8]. Alkylation of isomeric indoloindoles 3H,8H-indolo[5,4-e]indole (II), lH,6H-indolo[7,6-g]indole (III) and 3H,8H-indolo[4,5-e]indole (IV) was carried ont in 50% aqneons solution of NaOH nsing stechiometric quantity of alkylhalogenides, with ration of catalyst-tetrabutyl-ammonium and substrate 1 5 [8]. 

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