Showing papers on "Alkylation published in 1990"

Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents.

Abstract: Alkylating agents, because of their ability to react directly with DNA either in vitro or in vivo, or following metabolic activation as in the case of the dialkylnitrosamines, have been used extensively in studying the mechanisms of mutagenicity and carcinogenicity. Their occurrence is widespread in the environment and human exposure from natural and pollutant sources is universal. Since most of these chemicals show varying degrees of both carcinogenicity and mutagenicity, and exhibit compound-specific binding patterns, they provide an excellent model for studying molecular dosimetry. Molecular dosimetry defines dose as the number of adducts bound per macromolecule and relates the binding of these adducts to the human mutagenic or carcinogenic response. This review complies DNA alkylation data for both methylating and ethylating agents in a variety of systems and discusses the role these alkylation products plays in molecular mutagenesis.

An improved method for reductive alkylation of amines using titanium(IV) isopropoxide and sodium cyanoborohydride

Abstract: We now report that titanium(IV) isopropoxide is a mild and effective Lewis acid catalyst for the reductive alkylation of amines with ketones and aldehydes in the presence of acid-sensitive functional groups

Asymmetric Synthesis Utilizing External Chiral Ligands

Abstract: This review examines some typical examples that illustrate the significant developments reported recently, in which external chiral ligands have been used as asymmetric controllers in stoichiometric and catalytic amounts

Reaction products in hemoglobin and DNA after in vitro treatment with ethylene oxide and N-(2-hydroxyethyl)-N-nitrosourea.

Abstract: Reaction products with DNA and blood proteins have been used for monitoring human exposure to electrophilic compounds and metabolites. The formation of products with nucleophilic sites in DNA after treatment with such reagents has been well characterized (especially for alkylating agents). It is therefore of great importance to collect corresponding data for nucleophilic groups in proteins. The formation of reaction products in hemoglobin (Hb) and DNA was studied after in vitro treatment with ethylene oxide (EtO) and N-(2-hydroxyethyl)-N-nitrosourea (HOEtNU). In DNA N-7-(2-hydroxyethyl)guanine was the main product of EtO, whereas O6-(2-hydroxyethyl)guanine was much lower (0.5% of the alkylation of guanine-N-7). For HOEtNU O6-(2-hydroxyethyl)guanine was found to be 63% of N-7-(2-hydroxyethyl)guanine. These relative reactivities are in agreement with what has been reported for related alkylating agents. The main reaction products in Hb were 2-hydroxyethylations of cysteine, N-terminal valine, the two imidazole nitrogens in histidine and carboxylic groups. The reactivities of human, mouse and rat Hb towards EtO were compared. The main difference between species was the 12 and 170 times higher reactivity of cysteine in mouse and rat Hb, respectively, than in human Hb. As expected from relative reactivities of alkylating agents with model nucleophiles, products with cysteine dominated for EtO (except in human Hb) whereas for HOEtNU products with carboxylic groups were far larger than any other. Relative amounts of cysteine and carboxylic group alkylation in mouse Hb were compared with corresponding data for other alkylating agents. The comparison showed that these amounts were close to what could be expected from known reactivities of these compounds with model nucleophiles, but that sterical and other modifying factors have to be taken into account. Each compound gives therefore a species-specific pattern that might be used for tracing human exposure of unknown origin.

Reactions of trifluoromethyl bromide and related halides: part 10. Perfluoroalkylation of aromatic compounds induced by sulphur dioxide radical anion precursors

Abstract: Perfluoroalkylation of electron-rich aromatic compounds with trifluoromethyl bromide, or long-chain perfluoroalkyl iodides, was performed in the presence of sodium dithionite or zinc–sulphur dioxide. This alkylation occurred at the ortho and para positions relative to the amino or hydroxy substituent. Pyrroles were perfluoroalkylated regioselectively at the 2-position. This alkylation was interpreted as a radical aromatic substitution; the formation of the perfluoroalkyl radical can be induced by a single-electron transfer from sulphur dioxide radical anion to the perfluoroalkyl halide.

Development of a new acyl anion equivalent for the preparation of masked activated esters, and their use to prepare a dipeptide

Abstract: A new acyl anion equivalent, the protected hydroxymalonitrile 2, has been developed as a masked activated ester equivalent. Alkylation or allylation of 2a proceeded in high yields under mild basic or neutral conditions, respectively. Treatment of the tosylimine 18 with 2a gave the dipeptide 20 via the α-amino acid having a masked activated functionality

New Aspects of Stereoselective Synthesis of 1,3-Polyols

Abstract: Recent progress in the methodology for stereoselective synthesis of the 1,3-polyol functions is reviewed. Strategies for the synthesis of the extended 1,3-polyol chain are also described

Process for preparing long chain alkyl aromatic compounds

Abstract: Relatively long chain alkyl aromatic compounds are prepared by alkylating an alkylatable aromatic compound with a relatively long chain alkylating agent under alkylation reaction conditions in the pressure of a layered material as an alkylation catalyst. The layered material contains titanate in the layers and oxide pillars separating the layers. The layers also contain vacancies and/or metals incorporated therein.

Di-tert-butylcyclopentadiene and tri-tert-butylcyclopentadiene

Abstract: Synthese de tris-t-butyl-1,2,4 et de di-t-butyl-1,3 (1,4 ou 2,5) cyclopentadiene-1,3 par alkylation, avec catalyse transfert phase, de cyclopentadiene-1,3 avec le bromo-2 methyl-2 propane

DNA-directed alkylating ligands as potential antitumor agents: sequence specificity of alkylation by intercalating aniline mustards.

Abstract: The sequence preferences for alkylation of a series of novel parasubstituted aniline mustards linked to the DNA-intercalating chromophore 9-aminoacridine by an alkyl chain of variable length were studied by using procedures analogous to Maxam-Gilbert reactions. The compounds alkylate DNA at both guanine and adenine sites. For mustards linked to the acridine by a short alkyl chain through a para O- or S-link group, 5'-GT sequences are the most preferred sites at which N7-guanine alkylation occurs. For analogues with longer chain lengths, the preference of 5'-GT sequences diminishes in favor of N7-adenine alkylation at the complementary 5'-AC sequence. Magnesium ions are shown to selectively inhibit alkylation at the N7 of adenine (in the major groove) by these compounds but not the alkylation at the N3 of adenine (in the minor groove) by the antitumor antibiotic CC-1065. Effects of chromophore variation were also studied by using aniline mustards linked to quinazoline and sterically hindered tert-butyl-9-aminoacridine chromophores. The results demonstrate that in this series of DNA-directed mustards the noncovalent interactions of the carrier chromophores with DNA significantly modify the sequence selectivity of alkylation by the mustard. Relationships between the DNA alkylation patterns of these compounds and their biological activities are discussed.

Highly Diastereoselective Alkylation of Chiral Tin(II) Enolates onto Cyclic Acyl Imines, An Efficient Asymmetric Synthesis of Bicyclic Alkaloids Bearing a Nitrogen Atom Ring Juncture.

Abstract: An extremely short asymmetric synthesis of the 1-azabicyclic alkaloids involving pyrrolizidine, indolizidine, and quinolizidine skeletons is described. The key reaction used is a novel asymmetric alkylation of chiral tin(II) enolates of various 3-acyl-4 (S or R)-IPTTs onto cyclic acyl imines. This particularly mild alkylation procedure is highly general, exhibits high diastereoselectivity, and allows prediction of the absolute stereochemistry of the alkylation products

[2,3]-Wittig rearrangement of nonracemic (propargyloxy)acetic acids and esters. Synthesis of optically active 2,5-dihydrofurans

Abstract: Optically active propargyloxyacetic acids 4, available in ca. 90% ee through reduction of alkynones 2 with Chirald-LiAlH 4 followed by alkylation with chloroacetic acid, undergo highly stereoselective [2,3] rearrangement upon treatment with LDA in THF at -78°C to afford α-(S)-hydroxy-β-(R)-allenic acids with complete transfer of chirality and > 90% diastereoselectivity. The diastereomeric methyl ester derivatives 5a and 13 cyclize stereospecifically to trans and cis 1,5-dihydrofurans upon treatment with AgNO 3 -CaCO 3 , PhSeCl, or NBS

N-(9-phenylfluoren-9-yl)-.alpha.-amino ketones and N-(9-phenylfluoren-9-yl)-.alpha.-amino aldehydes as chiral educts for the synthesis of optically pure 4-alkyl-3-hydroxy-2-amino acids. Synthesis of the C-9 amino acid MeBmt present in cyclosporin

Abstract: Regioselective alkylation and reduction of N-(9-phenylfluoren-9-yl)serine-derived oxazolidine and oxazolidinone ketones stereoselectively provides γ-alkyl-β-hydroxy-α-amino diols that are oxidized to yield γ-alkyl-β-hydroxy-α-amino acids

Polyamine analogues with antitumor activity.

Abstract: A series of tetraamines derived from 1,8-diaminooctane was prepared and tested as antitumor agents. The reaction of 1,8-diaminooctane with acrylonitrile gave N,N'-bis(cyanoethyl)-1,8-diaminooctane, which was reduced to tetraamine 20. Alkylation of the terminal nitrogen atoms of the tetra-Boc derivative of this compound by methyl or ethyl halide followed by removal of the Boc groups gave the bis(alkyl)polyamines 26a and 26b, respectively. These three compounds exhibit promising antitumor activity in the mouse L1210 leukemia model. Coadministration of a polyamine oxidase inhibitor potentiated the antitumor activity.

Stabilities of trivalent metal complexes of phenolic ligands related to N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED)

Abstract: The stability constants and other equilibrium parameters of the trivalent metal ion complexes of three multidentate ligands have been determined: N,N'-bis(2-hydroxy-3,5-dimethylbenzyl) ethylenediamine-N,N'-diacetic acid; N,N'-bis(2-hydroxy-3-methyl-5-tert-butylbenzyl) ethylenediamine-N,N'-diacetic acid; and N,N'-bis(2-hydroxy-3,5-dimethylbenzyl)-N-(2-hydroxyethyl) ethylenediamine-N'-acetic acid. Alkylation of the aromatic ring significantly increases the basicity of the ligand, as measured by protonation constants, but lowers metal ion affinity, because of steric effects

Asymmetric alkylation of α-aryl substituted carbonyl compounds by means of chiral phase transfer catalysts. Applications for the synthesis of (+)-podocarp-8(14)-en-13-one and of (−)-Wy-16,225, a potent analgesic agent

Abstract: Asymmetric induction in the alkylation (alkyl halides and enones) of α-aryl substituted ketones, esters and lactones by means of CPTC has been evaluated. The catalysts used are the bromides of N-(p-trifluoromethyl) benzyl derivatives of cinchonine, cinchonidine, dihydrocinchonine and dihydrocinchonidine. The potential of the method is illustrated by the asymmetric synthesis of (+)-podocarp-8(14)-ene-13-one ( 13 ) and of (−)-Wy-16,225 ( 10 ), a bridged aminotetralin with potent analgesic properties.