Showing papers on "Diazomethane published in 1976"

Bile acid glucuronides, II[1]. Isolation and identification of a chenodeoxycholic acid glucuronide from human plasma in intrahepatic cholestasis.

Abstract: The isolation of a glucurono-conjugate of a bile acid has been performed from human plasma in a case of chronic intrahepatic cholestasis. By means of a series of chromatographic steps, esterification with diazomethane and acetylation a mixture of methylester polyacetates of steroid glucuronides was obtained, which could be separated by thin-layer chromatography. Methyl 7alpha-acetoxy-3alpha-O-(methyl 2, 3, 4-tri-O-acetyl-beta-D-glucopyranosyluronate)5beta-cholan-24-oate, synthesized via the Koenigs-Knorr condensation reaction, was used as reference substance. From comparison of the chromatogrphic behaviour and the mass spectrum of the natural compound and the synthetic product the structure of the bile acid derivative isolated from plasma could be established as a peracetylated methylester of chenodeoxycholic acid-3-beta-D-glucuronide.

Identification of enzyme-bound activated CO2 as carbonic-phosphoric anhydride: isolation of the corresponding trimethyl derivative from the active site of glutamine-dependent carbamyl phosphate synthetase

Abstract: The activated CO2 intermediate formed in the reaction catalyzed by glutamine-dependent carbamyl phosphate synthetase was identified as carbonic-phosphoric anhydride through the use of two independent procedures. The carboxy phosphate intermediate was reduced to formate by treatment with potassium borohydride. Although both free CO2 and the enzyme-bound activated CO2 are reduced to formic acid by borohydride, it was possible to selectively introduce a 14C label into the enzyme-bound activated CO2 and thus into the formic acid derived from it. Such [14C]formate formation required the presence of ATP, KCl, and the enzyme, and evidence was obtained that the [14C]formate found is not derived from carbamyl phosphate or from bicarbonate bound nonspecifically to the enzyme. When the enzyme was treated with L-2-amino-4-oxo-5-chloropentanoate (or cyanate), the formation of [14C]formate was increased about 2-fold, a finding consistent with the previous observation that such treatment effects a similar increase in the bicarbonate-dependent cleavage of ATP catalyzed by the enzyme. When reaction mixtures containing the enzyme, [gamma-32P]ATP, and [14C]bicarbonate were methylated by treatment with diazomethane, a labeled compound was formed which cochromatographed with authentic trimethyl carboxy phosphate. Equimolar quantities of 14C and 32P wer incorporated into the intermediate, thus confirming its identification as carboxy phosphate. Nonenzymatic transphosphorylation from ATP to bicarbonate to form carboxy phosphate was also detected by diazomethane trapping.

Reaction of diazoalkanes with 1-substituted 2, 4-dioxopyrimidines. Formation of O2, N-3 and O4-alkyl products.

Abstract: In non-aqueous solution, diazomethane and diazoethane react with the O2, O4 and N-3 sites of uridine, thymidine, 1-methyluracil and 1-methylthymine. Diazoethane has a higher affinity for alkylating oxygens than does diazomethane. The relative ratio of O2:O4:N-3 methyl products is 1:2:16 and of ethyl products the ratio is 1:1:2. When the diazoethane reaction is performed in neutral buffered solution, the same proportion of O2:O4:N-3 ethyl products is found, but the extent of reaction is very low. O2-alkylation greatly labilizes the glycosidic bond of thymidine and uridine toward acid hydrolysis. All O2 and O4 alkyl 1-substituted 2,4-dioxopyrimidines are dealkylated in weak acid but the O2 alkyl group is the more stable.

Die Synthese von 1,3‐disubstituierten Adamantanen

Abstract: Synthesis of 1,3-Disubstituted Adamantanes. A series of new 1-substituted 3-bromoadamantanes has been prepared. An improved method for the formation of cyclopropanes from olefins with diazomethane and copper salts is described.

Methylation of adenosine in strongly alkaline medium: Preparation and Properties of o'-methyl derivatives of adenosine and N6-methyladenosine.

Abstract: In strongly alkaline aqueous medium, 9-substituted adenines, including adenine nucleosides, are relatively resistant to alkylation of the ring nitrogens and the exocyclic amino group. This fact was utilized to obtain the various possible Omicron'-methyl derivatives of adenosine by dimethyl sulfate treatment of the latter in alkaline medium, followed by separation of the products on a Dowex OH-column. In strongly alkaline aqueous dimethyl sulfoxide, several derivatives additionally methylated on the amino group were obtained, including N6,O2'-dimethyladenosine, a component located recently at the 5' terminus of animal cell and viral mRNAs. The latter was also prepared by diazomethane methylation of N6-methyladenosine in the presence of SnCl2. Alkylation in alkaline medium possesses the advantage that the products are not limited to those involving etherification of cis hydroxyls and is applicable to adenine nucleosides with sugar components other than ribose. The properties of the various O'-methylderivatives, including proton magnetic resonance data, are presented in detail.

Direct N-methylation of 2-pyridylphosphonic acids by diazomethane

Abstract: N-Methylation of 2-pyridyiphosphonic acids is shown to involve direct attack rather than a route through O-methylation followed by rearrangement.

Studies of heterocyclic compounds. VIII. Synthesis and tautomerism of 2-hydroxypyrazolo(1,5-a)pyridine.

Abstract: 2-Hydroxypyrazolo[1,5-a]pyridine (I) was synthesized by reaction of ethyl 2-pyridylacetate (IV) with hydroxylamine-O-sulfonic acid I was shown to undergo nitrosation, nitration and bromination at C-3 position Methylation of I with diazomethane gave 2-methoxypyrazolo[1,5-a]pyridine (V), while methylation of I with dimethyl sulfate gave a mixture of V and 1-methyl-1,2-dihydropyrazolo[1,5-a]pyridin-2-one (VI) The enol form was found to be predominant tautomeric species of I in solution Treatment of I with acetic anhydride afforded 2-acetoxypyrazolo[1,5-a]pyridine (XIII) exclusively 1-Acetyl-1,2-dihydropyrazolo[1,5-a]pyridin-2-one (XIV) dose not seem to intervene in the formation of thermally stable O-acetylated product (XIII)

Chemistry of nitrosoimines. XV. Reactions of 3-substituted 2-nitrosoimino-2,3-dihydrobenzothiazoles with lithium aluminum hydride and diazo compounds.

Abstract: 3-Substituted 2-nitrosoimino-2,3-dihydrobenzothiazoles (1) were reduced with lithium aluminum hydride to give the corresponding thiazolone azines and bis[o-(N-substituted N-formylamino)phenyl] disulfides as major products. Reactions of 1 with some substituted diazomethanes gave the corresponding unsymmetrical azine N-monoxides (16) or azines (17) depending on the structure of the diazomethane.

Synthesis of sulphines from sulphur monoxide and diazoalkanes

Abstract: Sulphur monoxide, generated in situ from thiiran 1-oxides, reacts with diazomethane derivatives leading to thione S-oxides.

Synthesis, antimalarial activity, and phototoxicity of some benzo(h)quinoline-4-methanols.

Abstract: Nine alpha-dibutylaminomethylbenzo[h]quinoline-4-methanols were synthesized from the corresponding 1-amino-naphthalenes by the following sequence: 1-aminonaphthalene leads to 1H-benz[g]indole-2,3-dione leads to benzo[h]quinoline-4-carboxylic acid leads to acid chloride leads to bromomethyl ketone leads to epoxide leads to benzo[h]quinoline-4-methanol. Several acid chlorides substituted in the 3 position reacted incompletely with ethereal diazomethane but were efficiently converted, without isolation of the intermediates, to the bromomethyl ketones by reaction with ethoxymagnesium diethylmalonate, bromination, hydrolysis, and decarboxylation. Several compounds prepared, especially alpha-dibutylaminomethyl-2-(2',4'-dimethylphenyl)-3-methyl-6-chlorobenzo[h]quinoline-4-methanol, showed significant antimalarial activity against Plasmodium berghei in infected mice but were moderately phototoxic.

1, 2, 4-Triazoles. VII. Methylation of 1, 2, 4-Triazoles

Abstract: The methylations of twenty-five 1, 2, 4-triazoles with methyl iodide and diazomethane were studied and substituent effects on the product ratios are discussed. Methylation of 1, 2, 4-triazole and its symmetrically 3, 5-disubstituted derivatives occurred almost exclusively at the 1-position. These results are interpreted in terms of the α-effect of the α-diaza structures of the 1- and 2-positions in the 1, 2, 4-triazoles. Methylations of 3-substituted 1, 2, 4-triazoles with methyl iodide and diazomethane occurred preferentially at the N-1 atom, which is sterically less hindered. However, methylation of 3-α-pyridyl-1, 2, 4-triazole with diazomethane occurred preferentially at the N-2 atom next to the α-pyridyl group due to the particular space effect of the α-pyridyl group. Methylation of 3, 5-disubstituted 1, 2, 4-triazoles occurred predominantly at the vicinal nitrogen atom next to the electron-releasing group, but 3-α-pyridyl derivatives were methylated mainly at the vicinal nitrogen atom next to the α-pyridyl group.

The determination of warfarin in animal tissues by electron-capture gas-liquid chromatography

Abstract: A method is described for the quantitative analysis of warfarin residues in animal tissues. An extract is made with acetone, purified by column chromatography and solvent partitioning and the final ether solution is methylated with diazomethane. The methylation products have been identified, and electron-capture gas-liquid chromatography has been used to determine 4-methylwarfarin, with decachlorobiphenyl as an internal standard. The recoveries have been determined by radiochemical techniques and shown to be suitable for the routine determination of warfarin at the 0.1 µg g–1 level in tissue.

Spiro heterocyclic compound. II. Synthesis of spiro(indoline-3,3'-(5'-pyrazolin))-2-ones and related compounds.

Abstract: A spiro-heterocyclate, pyrazole-ring combined at the position-3 of indolin-2-ones was examined. 3-Phenacylideneindolin-2-ones (Ia-d) reacted with hydrazine hydrate to give the corresponding spiro [indoline-3, 3'-(5'-pyrazolin)]-2-ones (IIa-d). The reaction of 3-phen-acylidene-(Ia) and 3-acetonylideneindolin-2-one (If) with diazomethane afforded 4' benzoyl-(Va) and 4'-acetyl-spiro [indoline-3, 3'-(1'-pyrazolin)]-2-one (Vb), respectively. The decomposition of 1-pyrazolines (Va-b) by thermolysis or by reacting with HCI gave spiro [cyclopropane-1, 3'-indolin]-2'-ones (VIa and VIb), whereas during chromatography on alumina changed into 3-(α-benzoyl)-(VIIa) and 3-(α-acetyl) ethylideneindolin-2-one (VIIb), respectively. In addition, 3-(α-nitro) ethylideneindolin-2-one (VIII) reacted with diazomethane to give 1, 4'-dimethyl-4'-nitro-spiro [indoline-3, 3'-(1'-pyrazolin)]-2-one (IX), which being chromatographed on alumina gave 1, 4'-dimethyl-spiro [indoline-3, 3'-(3'H-pyrazol)]-2-one (X).

Human exposure to styrene. I. The gaschromatographic determination of urinary phenylglyoxylic acid using diazomethane derivatization.

Abstract: SummaryThe derivatization of phenylglyoxylic acid (PGA), a urinary styrene metabolite, gives with diazomethane under ordinary reaction conditions secondary products as expected from the behaviour of other α-keto acids. Thus reproducible quantitative analysis becomes difficult. It is shown that by proper selection of reaction conditions (low temperature, short reaction time) these secondary transformations can be inhibited and exclusive derivatization to the methylester is obtained. A quantitative determination of urinary PGA can be based on this derivatization procedure. However, this method is not considered suitable for routine monitoring due to the delicate reaction conditions necessary. The results are discussed with reference to a recently published procedure based on an unknown derivative of PGA.

Studies on the Syntheses of Heterocyclic Compounds. DCLXXI. An Alternative Total Synthesis of Yohimbine

Abstract: Birch reduction of 16-carboxy-15, 16, 17, 18, 19, 20-hexadehydro-17-methoxyyohimbane (XII), followed by esterification with diazomethane, gave 15, 17, 18, 20-tetradehydro-17-meth-oxy-16-methoxycarbonylyohimbane (XIII), which was converted into 15, 16-dehydroyohimbinone (II). This was correlated with yohimbine (IV) by the present authors.

Studies on the Syntheses of Heterocyclic Compounds. DCLXIII. The Reaction of Pyridone Derivatives with Diazoalkane

Abstract: The reaction of 3-carboxy-1, 2-dihydro-1-methyl-2-oxopyridine (V) with diazomethane afforded 6, 7-dihydro-1, 6-dimethyl-7-oxopyrazolo [3, 4-c] pyridine (VI), 4, 5, 6, 7-tetrahydro-1, 6-dimethyl-7-oxopyrazolo [3, 4-c] pyridine (VII), and 1, 2-dihydro-3-methoxycarbonyl-1, 4-dimethyl-2-oxopyridine (VIII). 1-Ethyl-6, 7-dihydro-3, 6-dimethyl-7-oxopyrazolo [3, 4-c] pyridine (XXI), 8a-ethoxycarbonyl-1, 4, 4a, 7, 8, 8a-hexahydro-3, 4, 7-trimethyl-8-oxopyrido [3, 4-c] pyridazine (XXII), and 3-ethoxycarbonyl-4-ethyl-1, 2-dihydro-1-methyl-2-oxopyridine (XXIII) were obtained from the reaction of compound (V) with diazoethane. The treatment of 4-carboxy-1, 2-dihydro-1-methyl-2-oxopyridine (XXVIII) with diazomethane gave 1, 2-dihydro-4-methoxycarbonyl-1-methyl-2-oxopyridine (XXIX), 6-methoxycarbonyl-3-methyl-2-oxo-3-azabicyclo [4. 1. 0] hept-4-ene (XXX), and 1, 2-dihydro-4-methoxycarbonyl-1, 3-dimethyl-2-oxopyridine (XXXI). The reaction of compound (XXIX) with diazoethane afforded 3-ethyl-1, 2-dihydro-4-methoxycarbonyl-1-methyl-2-oxopyridine (XXXII), 6α-methoxycarbonyl-3, 7β-dimethyl-2-oxo-3-azabicyclo [4, 1, 0]-hept-4-ene (XXXIII), and 1-ethyl-6-methoxycarbonyl-3, 7-dimethyl-2-oxo-3-azabicyclo [4. 1. 0] hept-4-ene (XXXIV). In case of the treatment of 5-carboxy-1, 2-dihydro-1-methyl-2-oxopyridine (XXXV) and 1, 5-dihydro-1, 5-dioxo-3H-oxazolo [3, 4-a] pyridine (XXXVIII) with diazomethane, 1, 2-dihydro-5-methoxycarbonyl-1-methyl-2-oxopyridine (XXXVI) and 1, 2-dihydro-6-methoxycarbonyl-1-methyl-2-oxopyridine (XXXIX) were obtained, respectively.

C-Nucleosides and related compounds. VII. Synthesis of carbocyclic analogues of C-nucleosides

Abstract: Condensation of lactone 1 and aminoguanadine provides the amino-triazole carbocyclic analogue of C-nucleoside 2a. Lead tetraacetate oxidation of the semicarbazone derivative 4 leads to the amino-oxadiazole derivative 5. Isoxazolines 11 and 12 are obtained by 1,3-dipolar addition of mesitonitrile oxide with the α,β-unsaturated ester 13. Addition of diazomethane onto ester 13 gives the pyrazoline 16 which can be oxidized with bromine to the corresponding carboethoxy-pyrazole 17. The latter is converted to the carboxamido-pyrazole 18 by treatment with ammonia.

1, 2, 4-Triazoles. VI. Methylation of 3-Phenyl-1, 2, 4-triazolin-5-one, 3-Phenyl-1, 2, 4-triazoline-5-thione, and Their Monomethylated Derivatives

Abstract: The product distributions resulting from methylation of 3-phenyl-1, 2, 4-triazolin-5-one (1a) and 3-phenyl-1, 2, 4-triazoline-5-thione (1b) and their monomethylated derivatives (2a, b-5a, b) with methyl iodide and diazomethane in various solvents were studied by nuclear magnetic resonance spectroscopy. The methylations of 1-methyl-3-phenyl-1, 2, 4-triazolin-5-one (3a), 5-hydroxy-2-methyl-3-phenyl-1, 2, 4-triazole (4a), and 4-methyl-3-phenyl-1, 2, 4-triazolin-5-one (5a), with methyl iodide in alkaline solution occurred preferentially at the N-atoms and afforded mainly 1, 4-dimethyl-3-phenyl-1, 2, 4-triazolin-5-one (9a), mesoionic anhydro-2, 4-dimethyl-5-hydroxy-3-phenyl-1, 2, 4-triazolium hydroxide (11a), and 9a, respectively. The product ratios on methylations of 3a, 4a, and 5a with diazomethane were affected variously by the type of solvent, the nucleophilicities of the four reaction sites, and the steric factor. Dimethyl sulfoxide (DMSO) increased O-methylation in all cases and especially with 4a, which exists in the OH form, methylation occurred almost exclusively at the oxygen atom in DMSO. The methylations of 1b and its N-methylated derivatives (3b-5b) with either methyl iodide or diazomethane gave S-methylated products predominantly in all the solvents used.

The chemistry of the indoleninones. III. Reactions of 2-(Methylthio)indoleninones with diazomethane

Abstract: The reactions of 2-(methy1thio)indoleninone [2-(methylthio)-3H-indol-3-one] and its 4-bromo and 6-bromo derivatives with diazomethane lead to the appropriate 2-(methylthio)spiro[3H-indole-3,2'- oxirans] and 3-methoxy-2-(methy1thio)quinolines in relative yields dependent upon the steric in- fluence of bromine when in the 4-position. P.m.r. studies on the 2-(methylthio)spiro[3H-indole-3,2'-oxirans] reveal a marked solvent depen- dence on the chemical shift values of the non-equivalent protons of the methylene group in the oxiran ring.