Showing papers on "Alkylation published in 1975"

The chemical effects of nucleic acid alkylation and their relation to mutagenesis and carcinogenesis.

Abstract: Publisher Summary This chapter discusses the studies relating to the chemical nature of alkylation, from the products of nucleoside alkylation to in vivo effects of alkylating agents that are oncogenic. The reactions of simple methylating agents with nucleosides, nucleotides, and polynucleotides have also been discussed in the chapter. More recent studies of the mechanism of alkylation by nitroso compounds and ethylating agents have shown that both qualitatively and quantitatively the site of alkylation is a function of both the type of reagent used and the conformation and milieu of the nucleic acid. However, translation of this body of knowledge to an understanding of the biological mechanism of alkylation-induced mutagenesis and carcinogenesis is difficult. Further studies of mutation in picornaviruses or their RNAs would be fruitful since these viral RNAs are also messenger RNAs and are directly translated, whereas in vivo studies, definitive information is still lacking as to whether alkylation of DNA, RNA, or perhaps protein, is the biologically important event.

Alkylation in presence of thermally modified crystalline aluminosilicate catalyst

Abstract: Process for the alkylation of aromatic hydrocarbons by contacting same with an olefin alkylating agent in a reaction zone maintained under conditions such that said alkylation is accomplished in the presence of a catalyst comprising a crystalline aluminosilicate zeolite, said zeolite having a silica to alumina ratio of at least about 12 and a constraint index, as hereinafter defined, within the approximate range of 1 to 12, said catalyst having been modified by prior thermal treatment to reduce the activity thereof, as determined by an alpha value, as described herein, to less than about 250 and preferably within the range of less than about 200 but greater than 10.

Two-phase reactions in the chemistry of carbanions and halocarbenes. A useful tool in organic synthesis

Abstract: Among numerous base-solvent systems usually applied for the generation of carbanions the two-phase system in which a concentrated aqueous sodium hydroxide solution in the presence of quaternary ammonium compounds acts as the proton acceptor seems to be particularly useful. Under these conditions, C-H acids up to 22 pK a value can be converted into carbanions which exist in the organic phase as ion-pairs with the quaternary ammonium cation. Though the concentration of the carbanions is very low, and does not exceed that of the catalyst, numerous reactions have been successfully performed under these conditions. Thus, alkylation of various C-H acids, such as arylacetonitriles, some esters, ketones, aldehydes, cyclopentadiene hydrocarbons etc. proceeds in this way with higher selectivity and yield as compared to the traditional conditions. The two-phase system is of particular advantage for the generation of trihalomethylanions and dihalocarbenes thereafter, as it allows us to carry out all the reactions typical for these species in the simplest and most effective manner. It is moreover mostly convenient for the reactions of some carbanions with aromatic nitrocompounds (substitution of halogen and nitro group or electron-transfer) which otherwise give rather poor results. And the latest so far recognized application of this system in carbanion chemistry is the reaction of halocarbanions and ylides leading to oxiranes, cyclopropanes and alkenes. The author's point of view is that the first common step of all these reactions, namely proton abstraction with the formation of a carbanion quaternary ammonium cation ion-pair, occurs on the phase boundary. The ion-pair thus formed penetrates inside the organic phase where all subsequent steps (reactions of carbanions with various electrophiles, formation and reactions of halocarbenes etc.) take place.

Pyrido(2,3-d)pyrimidine antibacterial agents. 3. 8-Alkyl- and 8-vinyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)pyrido(2,3-d)pyrimidine-6-carboxylic acids and their derivatives.

Abstract: The preparation and antibacterial activity of a series of the title compounds (21-73) are described. These compounds were prepared from the 2-methylthio derivatives 2 and 3 via the 2-methylthio-8-substituted compounds 4-20; compounds 4-20 easily underwent displacement reactions with a variety of piperazines to afford 2-(4-substituted or unsubstituted 1-piperazinyl) derivatives 21-56, of which 21, 22, 27 and 51 with unsubstituted piperazinyl group at position 2 are converted subsequently into 57-73 by alkylation, acylation, sulfonylation, or addition of isocyanates to the piperazine nitrogen. The hexahydro-1H-1,4-diazepinyl analog 74 was also prepared. The most active members in this series of compounds were found to be 8-ethyl- and 8-vinyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)pyrido(2,3-d)pyrimidine-6-carboxylic acids (22 and 51), both of which are more active in vitro and in vivo against gram-negative bacteria, including Pseudomonas aeruginosa, than piromidic acid (1). Structure-activity relationships are discussed.

Motor fuel production with fluid catalytic cracking of high-boiling alkylate

Abstract: High octane number motor fuel is produced by alkylating isobutane with an olefin to produce an alkylate separable into distinct low octane and high octane fractions, charging the low octane fraction to a fluidized catalytic cracking unit to generate more olefins which can be charged to the alkylation process to produce an increased quantity of high octane number alkylate.

Alkylation of enolate ions generated regiospecifically via organocopper reactions. Synthesis of decalin sesquiterpene valerane and of prostaglandin model systems.

Abstract: Das Dibromhexanon (I) wird durch die Organokupferreagenzien (II) in die Enolat- Ionen (III) ubergefuhrt.

Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines.

Abstract: Ethylation and isopropylation of guanine in alkaline solution, or of adenine in formic acid, by alkyl methanesulphonates gave the following products: 1-, N2-, 3-, O6-, 7- and 9-alkylguanines; 1-, 3-, 7- and 9-alkyladenines. The products were identified from their characteristic u.v-absorption spectra, by comparison with either known ethyladenines or with the corresponding known methyladenines, and were also characterized by mass spectrometry. Their chromatographic properties on paper, t.l.c. and various columns were determined. DNA was alkylated in neutral solution with 14C-labelled alkyl methanesulphonates and the ratios of the alkylpurines formed were obtained, and compared for alkylation by methyl, ethyl and isopropyl methanesulphonates and by N-methyl-N-nitrosourea. The extents of alkylation at O-6 of guanine relative to those at N-7 of guanine varied with the reactivity of the methylating agents according to the predictions of Swain & Scott (1953) relating nucleophilicity of the groups alkylated with the substrate constants of the alkylating agents. The relative extents of alkylation at N-3 of adenine did not follow this correlation.

Ion-pair formation as a source of enhanced reactivity of the essential thiol group of D-glyceraldehyde-3-phosphate dehydrogenase.

Abstract: The reactivity and the mode of activation of the essential – SH group (Cys-149) of d-glyceral-dehyde-3-phosphate dehydrogenase have been studied by means of a spectrophotometric method [Polgar, L., FEBS Lett. 38, 187–190 (1974)], capable of detecting the dissociated form of the thiol group in proteins. Alkylations of Cys-149 of NAD-free d-glyceraldehyde-3-phosphate dehydrogenase with iodoacetamide and iodoacetate were investigated. The corrected absorbance change on alkylation at 250 nm (which is a direct parameter of the dissociation of the thiol group) and the alkylation rate were determined as a function of pH. The pH profiles of both dissociation and alkylation rate of Cys-149 conform to doubly sigmoid curves. All these curves implicate two ionizing groups (pK1= 5.5, pK2= 8.2). It is concluded that there are two reactive forms of the –SH group in the apoenzyme between pH 5 and 10. One reactive form corresponds to the free mercaptide ion. The other can be identified with an ion-pair composed of a mercaptide ion and some base, possibly the imidazolium group of His-176. The ion-pair has lower molar absorption coefficient and nucleophilicity than the free mercaptide ion. The two reactive forms are transformed into each other with pK2= 8.2. The ion-pair decomposes to a nondissociated thiol group and a protonated base with pK1= 5.5. In the presence of NAD, only the pH-rate profile of alkylation of d-glyceraldehyde-3-phosphate dehydrogenase was measured (at 370 nm). Using iodoacetamide as alkylating agent we also obtained a doubly sigmoid curve. A slight downward shift on pK1 and an upward shift in pK2 indicate that the ion-pair exists in a somewhat wider pH-range in the enzyme-coenzyme complex. An increase in the ionic strength of the reaction mixture from 0.09 to 0.45 M does not abolish the doubly sigmoid character of the curves determined either in the presence or in the absence of NAD.

Synthesen mit α‐metallierten Isocyaniden, XXIX. Höhere Aminosäuren durch Alkylieren von α‐metallierten α‐Isocyan‐propionsäure‐ und ‐essigsäureestern

Abstract: Aus α-Isocyanpropionsaure-athylester (1a) erhalt man uber die α-metallierten Derivate (2a) mit Alkylierungsmitteln (3) hohere 1-Isocyan-1-methyl-1-alkancarbonsaure-athylester (4). Mit Isocyanessigsaure-athylester (1b) und 3 dominiert die Bis-Alkylierung zu den 1-Isocyan-1-alkancarbonsaureestern 5, mit 1,2-Dibromathan, Bis(2-chlorathyl)-ather und 1,4-Dibrombutan isoliert man die 1-Isocyan-1-cycloalkancarbonsaureester 8, 9, und 10. Beim Isocyanessigsaure-tert-butylester (1c) ist die Mono-Alkylierung zu 6 begunstigt. Die Isocyan-Gruppe hydrolysieren. D.h. die baseninduzierte Alkylierung niederer α-Isocyan-alkancarbonsaureester, gekoppelt mit der Hydrolyse der Isocyan-Gruppe, stellt ein neues Verfahren dar zum Aufbau hoherer Aminosauren. Syntheses with α-Metalated Isocyanides, XXIX. Higher Amino Acids by Alkylation of α-Metalated Ethyl α-Isocyanopropionate and Alkyl Isocyanoacetates Ethyl α-isocyanopropionate (1a) reacts with alkylating agents (3) via the α-metalated derivatives 2a to give higher ethyl α-isocyano-α-methylalkanoates (4). In the reaction of ethyl isocyanoacetate (1b) with 3 bis-alkylation dominates to yield 5. 1,2-Dibromoethane, bis(2-chloroethyl) ether, and 1,4-dibromobutane react with 1b or 1c to form the 1-isocyano-1-cycloalkanecarboxylic esters 8, 9, or 10. With tert-butyl isocyanoacetate (1c), however, monoalkylation occurs to give 6. The isocyano group in the alkylated products can be converted by mild acid hydrolysis to the N-formylamino or amino group. Thus the base-induced alkylation of lower alkyl α-isocyanoalkanoates followed by acid hydrolysis represents a novel route to higher amino acids.

Carboxymethylation of Horse‐Liver Alcohol Dehydrogenase in the Crystalline State

Abstract: Horse liver alcohol dehydrogenase (isozyme EE) in the crystalline state was alkylated with iodoacetate under conditions resulting in the single substitution of Cys-46, which is a ligand to the active-site zinc atom. Alkylation was facilitated by the prior formation of a complex with imidazole bound to the zinc atom. Extent and specificity of the reaction were determined by use of 14C-labelled iodoacetate and by analyses of radioactive peptides after cleavage with trypsin. Ternary complexes of the enzyme with coenzymes and inhibitors effectively protected the protein against alkylation. ADP-ribose, Pt(CN)2-4, 1,10-phenanthroline, Au(CN)-2 and AMP also prevented alkylation with decreasing effectiveness. Crystallographic studies of the alkylated enzyme show that the carboxymethylated sulfur atom of Cys-46 is still liganded to the active-site zinc atom and that the iodide ion liberated during alkylation is bound as the fourth ligand to zinc, displacing imidazole. Crystallographic analyses were also performed of the binding of AMP and Pt(CN)2-4 to the enzyme. It was found that Arg-47 interacts with the phosphate moiety of the nucleotide. Lys-228 and Arg-47 interact in the platinate complex with the bulky anion, the center of which coincides with the position of the nucleotide phosphate. Some of the cyano-ligands to platinum occupy a crevice between the coenzyme phosphate binding site and the active-site zinc atom. The results of the combined studies on primary and tertiary structures confirm previous suggestions that iodoacetate enters the active site via reversible binding to an anion-binding site. This site interacts with the negatively charged groups of the coenzyme as well as with ADP-ribose, Pt(CN)2-4 and to a lesser extent Au(CN)-2 and AMP, which therefore prevent the reversible binding of iodoacetate. 1,10-Phenanthroline does not block the binding site but interferes with alkylation presumably by changing the coordination of zinc. Identification of this labelled residue in both chemical and crystallographic studies correlates the primary and tertiary structures. Characterizations of the active-site zinc region and the general anion-binding site are also presented.

Alkylation in presence of phosphorus-modified crystalline luminosilicate catalyst

Abstract: Process for the alkylation of aromatic hydrocarbons by contacting same with an olefin alkylating agent in a reaction zone maintained under conditions such that said alkylation is accomplished in the vapor phase and in the presence of a catalyst comprising a crystalline aluminosilicate zeolite, said zeolite having a silica to alumina ratio of at least about 12 and a constraint index, as hereinafter defined, of from 1 to 12, said catalyst having been modified by the addition thereto of phosphorus in an amount of at least about 0.5 percent by weight.

Electrochemical reactions of organic compounds in liquid ammonia. III. Reductive alkylation of quinoline

Abstract: The electrochemical behavior of quinoline in anhydrous liquid ammonia was investigated by cyclic voltammetry and controlled potential coulometry. In the absence of added alkylating agent, quinoline is reduced in two steps to yield the radical anion and dianion both of which undergo further chemical reaction. The radical anion species dimerizes to form the dimeric dianion which is stable in the medium and can be reversibly reoxidized back to parent compound. The second-order rate constant for this dimerization reaction was found to be 1.5 X I O 2 I./mol sec at -4OOC. In the presence of ethyl bromide or n-butyl bromide, reductive alkylation proceeds via an ECEC mechanism to yield approximately equal quantities of the 1,2-dihydro1,2-dialkyl and 1,4-dihydro1.4-dialkyl derivatives. Differences in product composition between chemical reduction with lithium and electrochemical reduction are explained Recently there has been an upsurge of interest in the study of reductive alkylation reactions in nonaqueous solvents because of their possible applications to organic synthesis. Previously, this technique has been used to prepare a variety of monoand dialkyl derivatives by chemically reducing an unsaturated hydrocarbon with an alkali metal in liquid ammonia, followed by quenching of the reaction mixture with an alkyl halide.'-4 In more recent work, these reactions have been performed in the nonaqueous solvents dimethylformamide (DMF) and acetonitrile (AN) with electrochemical reduction of the parent An advantage i n this procedure over alkali metal reduction is that both reactants can be present in solution simultaneously since selective reduction of the unsaturated compound can be obtnincd by proper adjustment of the electrode potential. With the electrochemical procedure, the scope of the reaction has been broadened to include reduction of unsaturated carbon-oxygen, carbon-nitrogen, and nitrogen-oxygen bonds, while the use of acid chlorides or acid anhydrides as electrophiles has led to the preparation of certain acyl derivatives in addition to the alkyl derivatives available from reaction with alkyl halides. A competing protonation reaction frequently accompanies the alkylation reaction in DMF and AN, producing a product mixture consisting of diprotonated, monoalkylated, and dialkylated derivatives, with the dialkyl derivative often occurring in very low yield. A higher yield of the alkyl derivatives as well as a better understanding of the alkylation reaction would be obtained if protonation could be eliminated. For this reason, a study of this reaction with Smith, Bard / Reductire Alkylation of Quinoline

Simple route to mono-, di-, and tri-substituted allenic compounds

Abstract: Allenic compounds can be prepared in high yields without appreciable rearrangement by alkylation of allenic lithium reagents.