Showing papers on "Alkylation published in 1997"

Process for the preparation of 2'-O-alkyl purine phosphoramidites

Abstract: Processes for preparing 2'-O-alkylated guanosine, uridine, cytidine, and 2,6-diaminopurine 3'-O-phosphoramidites include the steps of alkylating nucleoside precursors, adding suitable blocking groups and phosphitylating. For the guanosine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effected on 2,6-diamino-9-(β-D-ribofuranosyl)purine followed by deamination. For uridine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effect on a dialkyl stannylene derivative of uridine. For cytidine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effected directly on cytidine. Alkylation is effected directly upon 2,6-diaminopurine.

Synthesis of chitosan derivatives with quaternary ammonium salt and their antibacterial activity

Abstract: N-alkyl chitosan derivatives were prepared by introducing alkyl groups into the amine groups of chitosan via Schiff’s base intermediates. Quaternization of the N-alkyl chitosan derivatives were carried out using methyl iodide to produce water soluble cationic polyelectrolytes, novel chitosan derivatives with quaternary ammonium salt. Their antibacterial activities against S. aureus were explored by the viable cell counting method in acetate buffer(pH 6.0). The antibacterial activities of the chitosan derivatives with quaternary ammonium salt increased with increase in the chain length of the alkyl substituent, and this increased activity could be ascribed to the contribution of the increased hydrophobic properties of the derivatives.

Structural Requirements for Binding of Anandamide-Type Compounds to the Brain Cannabinoid Receptor

Abstract: In order to establish the structural requirements for binding to the brain cannabinoid receptor (CB1), we have synthesized numerous fatty acid amides, ethanolamides, and some related simple derivatives and have determined their Ki values. A few α-methyl- or α,α-dimethylarachidonoylalkylamides were also examined. In the 20:4, n-6 series, the unsubstituted amide is inactive; N-monoalkylation, at least up to a branched pentyl group, leads to significant binding. N,N-Dialkylation, with or without hydroxylation on one of the alkyl groups, leads to elimination of activity. Hydroxylation of the N-monoalkyl group at the ω carbon atom retains activity. In the 20:x, n-6 series, x has to be either 3 or 4; the presence of only two double bonds leads to inactivation. In the n-3 series, the limited data reported suggest that the derived ethanolamides are either inactive or less active than comparable compounds in the n-6 series. Alkylation or dialkylation of the α carbon adjacent to the carbonyl group retains the level...

Kinetic and Theoretical Investigation of the Gas-Phase Ozonolysis of Isoprene: Carbonyl Oxides as an Important Source for OH Radicals in the Atmosphere

Abstract: Kinetic measurements as well as B3LYP/ and MP2/6-31G(d,p) calculations provide evidence that carbonyl oxides formed in the gas-phase ozonolysis of alkylated alkenes are an important source of OH radicals. In the gas-phase ozonolysis of propene, cis-2-butene, trans-2-butene, tetramethylethene, and isoprene, 18, 17, 24, 36, and 19% OH radicals (relative to reacted ozone, error margin ≤4%) are measured using CO as a scavenger for OH. The quantum chemical calculations show that OH radical production depends on syn positioned methyl (alkyl) groups and their interaction with the terminal O atom of a carbonyl oxide. For example, in the gas-phase ozonolysis of ethene only 5% OH radicals are measured while for a carbonyl oxide with syn-positioned methyl (alkyl) group, a much larger amount of OH radicals is formed. This is due to the fact that 1,4 H migration and the formation of an intermediate hydroperoxy alkene, that is prone to undergo OO bond cleavage, is energetically more favorable than isomerization to diox...

Scandium(III) Triflate-Catalyzed Friedel−Crafts Alkylation Reactions

Abstract: The Sc(OTf)3-catalyzed Friedel−Crafts alkylation reaction with an alcohol, an arenecarbaldehyde or an arenecarbaldehyde acetal as the alkylating agent affords a diarylmethane or an allylbenzene derivative highly selectively. The salient feature of this reaction is that only a catalytic amount of Sc(OTf)3 can effect the reaction. Furthermore, Sc(OTf)3 is recoverable and reusable after the synthetic reaction. The Sc(OTf)3-catalyzed benzylation using an arenecarbaldehyde and 1,3-propanediol or their acetal affords diarylmethane as a sole product in excellent yields in sharp contrast to the original Friedel−Crafts reaction. Since no reaction occurs in the absence of 1,3-propanediol, the reaction is considered to proceed through a redox process including a hydride shift. The hydride shift mechanism is strongly supported by the experimental evidence. The reaction of benzaldehyde with benzene in the presence of 1,3-propanediol-1,1,3,3,-d4 gives rise to the deuterium incorporation into the benzylic carbon of diph...

Highly Practical Methodology for the Synthesis of d- and l-α-Amino Acids, N-Protected α-Amino Acids, and N-Methyl-α-amino Acids

Abstract: Full details are provided for an exceedingly practical method to synthesize d- and l-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids, employing as a key step the asymmetric alkylation of pseudoephedrine glycinamide (1) or pseudoephedrine sarcosinamide (2). Practical procedures for the synthesis of 1 and 2 from pseudoephedrine and glycine methyl ester or sarcosine methyl ester, respectively, are presented. Optimum protocols for the enolization and subsequent alkylation of 1 and 2 are described. Alkylation reactions of 1 and 2 are found to be quite efficient with a wide range of alkyl halide substrates, and the products are formed with high diastereoselectivity. The products of these alkylation reactions are hydrolyzed efficiently and with little to no racemization simply by heating in water or water−dioxane mixtures. This protocol provides an exceedingly practical method for the preparation of salt-free α-amino acids of high enantiomeric purity. Alternatively, the alkylation products m...

[12] Reductive alkylation of lysine residues to alter crystallization properties of proteins.

Abstract: Publisher Summary This chapter discusses the reductive alkylation of lysine residues to alter the crystallization properties of proteins. Chemical modification has played an essential role in the development of protein function. The reductive alkylation of lysine residues involves the initial formation of a Schiff base between the ɛ-amino group of a lysine residue and a ketone or aldehyde that is then reduced to a secondary or tertiary amine. In principle, a wide variety of alkyl moieties can be added to an amino group by reductive alkylation. In practice, the majority of cases employing this chemical modification have focused on adding methyl groups using formaldehyde because of the greater reactivity of formaldehyde than other ketones or aldehydes and because this modification has the mildest effect on the biochemical properties of a protein. The protocols described in the chapter are designed for complete modification of all available lysine residues. Amino acid analysis is the best way of determining the degree of modification of the lysine residues after reductive alkylation. It has the advantage of quantitatively defining the number of non-, mono-, di-, and tri-methylated lysine residues. It reveals the presence of any side reactions with other reactive amino acid side chains in a protein.

Synthesis of functionalised fluorescent dyes and their coupling to amines and amino acids

Abstract: A series of novel functionalised benzophenoxazinones, analogues of Nile Red, is prepared and their fluorescence properties evaluated. The ring system is prepared by reaction of 5-diethylamino-2-nitrosophenol with 1,6-dihydroxynaphthalene followed by alkylation of the 2-hydroxy group with 6-bromohexanoic acid derivatives. Subsequent ester cleavage under a variety of conditions gives the acid 6. Replacement of the 9-diethylamino group with the N-ethyl-(3-sulfonylpropyl)amino group is carried out to increase water solubility and the resulting dye 14 has similar fluorescence properties. The acid 6 is coupled to a range of amino compounds.

Alkylation reactions in near-critical water in the absence of acid catalysts

Abstract: We report successful alkylation reactions in near-critical water in the absence of added acid catalysts Water has a strong tendency to ionize as the temperature is increased, allowing water in the near-critical region (250−350 °C) to act as an effective acid catalyst By simultaneously employing near-critical water as the reaction solvent and catalyst, the need for environmentally hazardous organic solvents and acid catalysts is eliminated The high hydronium ion content of near-critical water proved to be sufficient to synthesize a variety of substituted phenols with tertiary, secondary, and even primary alcohols The reaction products for each of these reactions are reported

Dihydro(alkylthio)(naphthylmethyl)oxopyrimidines: Novel non-nucleoside reverse transcriptase inhibitors of the S-DABO series

Abstract: Novel compounds related to 2-(cyclohexylthio)-3,4-dihydro-5-methyl-6-(3-methylbenzyl)-4-oxopyrimidine (3c, MC 639) have been synthesized and tested as inhibitors of human immunodeficiency virus type-1 (HIV-1). Reaction of thiourea with ethyl arylmethylacetoacetates furnished 5-alkyl-6-(arylmethyl)-3,4-dihydro-2-mercapto-4-oxopyrimidines which were then alkylated at the sulfur atom to afford the required 2-alkylthio or 2-cycloalkylthio derivatives (S-DABOs). Chemical modifications at N-3, C-4, and C-6 of the pyrimidine ring were attempted with the aim of improving antiretroviral activity. In particular, replacement of the benzyl group with the 1-naphthylmethyl moiety enhanced the activity of S-DABOs, whereas N-3 alkylation and C=O transformation into C=S at position 4 of the pyrimidine ring led to compounds devoid of anti-HIV-1 activity. Lower activity was generally observed when 1-naphthylmethyl was replaced by the isomeric 2-naphthylmethyl moiety. The most active compounds showed activity in the low micromolar range with EC 50 values comparable to that of nevirapine.

Surface Species Formed and Their Reactivity during the Alkylation of Toluene by Methanol and Dimethyl Ether on Zeolites As Determined by in Situ 13C MAS NMR

Abstract: 13C MAS NMR has been performed in situ to investigate the mechanism of toluene alkylation with methanol (MeOH) or dimethyl ether (DME) at 433 K over H−ZSM-11 catalyst. The reaction protocol used al...

Solid phase synthesis of 3,4-disubstituted-7-carbamoyl-1,2,3,4-tetrahydroquinoxalin-2-ones

Abstract: The solid phase synthesis of 3,4-disubstituted-7-carbamoyl-1,2,3,4-tetrahydroquinoxalin-2-ones 8 is described. 4-Fluoro-3-nitrobenzoic acid is tethered to a solid support via the acid group. Aromatic substitution of the resin-bound aryl fluoride with an α-amino ester is carried out in the presence of DIEA in DMF. The reduction of the aryl nitro group with SnCl2·H2O and subsequent intramolecular cyclization result in the formation of the core quinoxalinone. Selective alkylation at the N-4 position of the quinoxalinone is accomplished with alkyl halides in the presence of K2CO3. The desired products are cleaved from solid supports and obtained in from 32 to 93% isolated yields.

Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine

Abstract: The highly diastereoselective potassium in ammonia reduction−ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (−)-eburnamonine (4) and (−)-aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer−Villiger oxidation 7 → 8; Baeyer−Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at −55 °C gave an 18:1 mixture of 17 and its C(3) β-epimer in 93% yield. The oxidation of alcohol 18 containing sensi...

Supercritical-Phase Alkylation Reaction on Solid Acid Catalysts: Mechanistic Study and Catalyst Development

Abstract: Alkylation reaction on a zeolite catalyst was conducted in supercritical phase isobutane or isopentane, which was a reactant as well. Compared to the reactions conducted in a liquid phase or gas ph...

Facile, Regioselective Synthesis of Highly Solvatochromic Thiophene-Spaced N-Alkylpyridinium Dicyanomethanides for Second-Harmonic Generation

Abstract: The facile and clean synthesis of a novel class of highly solvatochromic chromophores 1 is reported. Compounds 1 are push−pull systems containing a negatively charged dicyanomethanide as a donor group and a positively charged N-alkylpyridinium as an acceptor group. The terminal polar functions are spaced by a thiophene-based moiety containing one or two heterocyclic rings and none, one, or two ethylene bridges. Chromophores 1 have been obtained through a general synthetic scheme involving, as the last step, the 100% regioselective alkylation of the precursor bidentate anions 2, where two competing nucleophilic sites, one neutral at the pyridic nitrogen and one anionic at the carbanionic carbon of the dicyanomethanide group, are present. The unprecedented highly regioselective attack of the alkylating agent onto the neutral pyridic nitrogen rather than the highly charged carbanionic carbon has been also confirmed in the case of the intermolecular competition. Multinuclear (13C and 15N) NMR spectroscopy has...

Acid zeolites as catalysts in organic reactions. tert-Butylation of anthracene, naphthalene and thianthrene

Abstract: Liquid phase tert-butylation of anthracene, naphthalene and thianthrene to afford 2-tert-butyl plus 2,6- and 2,7-di tert-butyl derivatives were carried out at atmospheric pressure and moderate temperatures (below 100°C) in the presence of a series of large pore zeolites and mesoporous aluminosilicates including HY-100 (Si/Al 2.6), HY-D1 (Si/Al 2.75), HY-D2 (Si/Al 15), Hβ, HMor and MCM-41. The activity increases from MCM-41 and Mor to β and Y zeolites, the latter being the most active catalysts. In addition, HY zeolites are much more efficient as catalysts than p-toluenesulfonic acid under the same reaction conditions. As alkylating reagent tert-butyl alcohol was employed in isooctane or carbon tetrachloride. It was found that isooctane itself is a powerful and convenient reagent for the tert-butylation. Mechanistic studies using radical scavengers indicates that in the isooctane alkylation tert-butyl cation is the sole intermediate involved. In the case of thianthrene, the concomitant formation of the thianthrenium radical cation during the alkylation reaction has been observed.

Introduction of a Long Alkyl Side Chain to Poly(benzimidazole)s. N-Alkylation of the Imidazole Ring and Synthesis of Novel Side Chain Polyrotaxanes

Abstract: NaH promoted deprotonation of the NH group in poly(benzimidazole)s, (−ImC6H4−)n (1a, Im = 5,5‘-dibenzimidazole-2,2‘-diyl), [−Im(CH2)8−]n (2a), and [{−Im(CH2)11O(CH2)11}0.91{Im(CH2)10−}0.09]n (3a) followed by addition of Br(CH2)12O(CO)CH2CPh3 causes substitution of the NH hydrogen of the parent polymer with the (CH2)12OCOCH2CPh3 group. The produced respective poly(benzimidazole) derivatives, 1b, 2b, and 3b, contain the N-alkylated imidazole group with a high content (85−91%) in the main chain and show high solubility in organic solvents. 1H NMR spectra of 1b−3b reveal that 91, 91, and 85% of the respective imidazole rings are N-alkylated. When the same reaction is carried out in the presence of trimethyl-β-cyclodextrin (TMe-β-CD), the reaction gives a new type of polymer (1c, 2c, and 3c, respectively), side chain polyrotaxanes. TMe-β-CD is incorporated in 21% and 57% of the side chains of 1c and 2c, while every side chain of 3c threads through two TMe-β-CDs. A GPC trace of 3c supports the formation of the ...

Synthesis and Evaluation of CC-1065 and Duocarmycin Analogues Incorporating the Iso-CI and Iso-CBI Alkylation Subunits: Impact of Relocation of the C-4 Carbonyl

Abstract: The synthesis of 2-(tert-Butyloxycarbonyl)-1,2,9,9a-tetrahydrocyclopropa[c]benzo[f]indol-8-one (31, N-BOC-iso-CBI) and 1-(tert-Butyloxycarbonyl)-4-hydroxy-3-[[(methanesulfonyl)oxy]methyl]-2,3-dihydroindole (19, seco-N-BOC-iso-CI) containing an isomeric structural modification in the CC-1065 and duocarmycin alkylation subunits and their incorporation into analogues of the natural products are detailed. The approach was based on a directed ortho metalation of an appropriately functionalized benzene (13) or naphthalene (24) precursor to regiospecifically install iodine at the C-2 position. Conversion of these respective intermediates to the dihydroindole skeleton utilized an established 5-exo-trig aryl radical cyclization onto an unactivated alkene with subsequent TEMPO trap or the more recent 5-exo-trig aryl radical cyclization onto a vinyl chloride for direct synthesis of the immediate precursors. Closure of the activated cyclopropane to complete the iso-CBI nucleus was accomplished by a selective ortho sp...