Heterocyclization of Derivatives of 4-Oxoalkanoic Acids to 1,5-Disubstituted Pyrrolin-2-ones

Conditions were developed for the synthesis and production of 1-aryl-5-alkyl(aryl)-3H- and 1-aryl-5-alkyl(aryl)-5H-pyrrolin-2-ones from the amides and esters of 4-oxoalkanoic acids. It was established that the yield and ratio of the 3H and 5H isomers depend on the substrate employed in the reaction.     

Surface-Mediated Synthesis of O-Alkyl 2-Methoxyethyl Alkylphosphonates Under Solvent Free Conditions: Potential Marker of Nerve Agents

This article describes rapid and efficient surface mediated synthesis of O-alkyl 2-methoxyethyl alkylphosphonates from alkylphosphonic acids and alcohols using dicyclohexyl carbodiimide (DCC)-Celite as a solid support. These compounds are markers of nerve agents. 2-Methoxyethyl methylphosphonic acids (2a–d) were reacted with various alcohols to yield O-alkyl 2-methoxyethyl alkylphosphonates (AMEAPs, 3a–m). This synthetic method has advantages over other methods in terms of selectivity, shorter reaction time, high yield, and easy work-up.     

α- and β-cyclodextrin complexes with n-alkyl carboxylic acids and n-alkyl p-hydroxy benzoates. A molecular mechanics study of 1:1 and 1:2 associations

Molecular mechanics (MM) methods were employed to evaluate stabilization upon formation of inclusion compounds between two different guest molecules and α- and β-cyclodextrins (CDs) for two different stoichiometries 1:1 and 1:2. The two guest molecules studied were n-alkyl carboxylic acids and n-alkyl p-hydroxy benzoates with variety of chain lengths. The computed stability for the inclusion compounds between α-CDs and n-alkyl carboxylic acids reproduced experimental data reported in the literature. The transition between 1:1/1:2 complexes occurred at an alkyl chain length of n_C=9. It was previously demonstrated by diffusion coefficients measures that a stable 1:2 stoichiometry inclusion compound could be formed between n-alkyl p-hydroxy benzoates and α-CD for the chain length n_C>4. The computed results reproduced the experimental ones. The combination between OPLS and GB/SA resulted in better agreements with experiments than those obtained with MM2 and MM3.     

Design, synthesis and utilization of a novel coupling reagent for the preparation of O-alkyl hydroxamic acids

An efficient novel reagent, phosphoric acid diethyl ester 2-phenyl-benzimidazol-1-yl ester, was designed, and synthesized and its applicability was demonstrated for the preparation of O-alkyl hydroxamic acids. The O-alkyl hydroxamic acids of N-protected amino acids were also synthesized. The enantiomeric purity of the synthesized compounds were measured using chiral HPLC and the degree of racemization was found to be negligible.     

Lewis acid-catalyzed hetero Diels–Alder cycloadditions of 3-alkyl, 3-phenyl and 3-carboxylated 2H-azirines

Activation by Lewis acids of 3-alkyl and 3-phenyl 2H-azirines promotes their participation in hetero Diels–Alder reactions with a variety of dienes. This methodology circumvents the previous requirement of an electron-withdrawing carboxyl moiety at the 3-position of the 2H-azirine.     

Synthese de β-ethoxycarbonyl λ-lactones

β-ethoxycarbonyl β, λ-insaturated λ-lactones 2 are easily prepared by dehydration of β-acyl β-ethoxycarbonyl α-alkyl propionic acids. Otherwise the condensation of these acids with allylzinc reagents produces β-ethoxycarbonyl λ-lactones 3 with a β-ethylenic carbon chain branched on the λ-carbon of the lactone.     

Enantioselective hydrolysis of nitriles and amides using an immobilised whole cell system

An immobilised whole cell catalyst SP361 has been shown to hydrolyse a range of 2-alkyl arylacetonitriles 1a–3a and amides 2b, 3b with good to excellent enantioselectivity. The absolute configuration of the derived amides and/or carboxylic acids shows remarkable changes according to the structure of the nitrite substrate.     

Highly diastereoselective preparation of anti-α,β-dialkyl β-amino acids containing natural α-amino acid side chains

An efficient synthesis of anti-2-alkyl β³-amino acids was developed starting from the fully protected β³-amino acids. The strategy allows the introduction of the side chain of natural α-amino acids such as Ala, Phe and Ser at the C-2 position, with high diastereoselectivity. The preparation of 2-methyliden-β³-amino acids is also reported. This methodology does not need the use of expensive chiral reagents and/or chiral auxiliaries, and leads to compounds with orthogonal protecting groups.     

Synthesis of 5-(perfluoroalkylmethyl)-1,3-dioxolan-4-ones

Acid catalysed condensation of F-alkyl α-hydroxy acids with simple aldehydes or ketones gave F-alkyl 1,3-dioxolan-4-ones. When BF₃,OEt₂ was used as the catalyst, the condensation products were obtained in moderate to good yields and the “cis” isomers are largely favoured, while with HOTs/H₂SO₄ as catalyst, poor yields and lower stereoselectivities were observed.     

Synthesis of 5-alkyl(aryl)sulfanyl-4-chloro-3-trichloromethyl-1,2-thiazoles and 5-Alkyl(aryl)sulfanyl-4-chloro-1,2-thiazole-3-carboxylic acids

Butane-, phenylmethane-, and benzenethiols reacted with 4,5-dichloro-3-trichloromethyl-1,2-thiazole in the presence of sodium ethoxide to give the corresponding 5-alkyl(aryl)sulfanyl-4-chloro-3-trichloromethyl-1,2-thiazoles. The reaction of 4,5-dichloro-1,2-thiazole-3-carboxylic acid with the same thiols under similar conditions resulted in the formation of sodium 4,5-dichloro-1,2-thiazole-3-carboxylate, while in the presence of pyridine 5-alkyl(aryl)sulfanyl-4-chloro-1,2-thiazole-3-carboxylic acids were obtained.     

Heterocyclic Analogs of Prostaglandins: I. Synthesis of 3-Alkyl(Aralkyl)-2,5-dihydrofuran-2-ones as Synthons for 11-Deoxy-10-oxaprostanoids

3-Acyl(arylmethyleneacyl)tetronic acids were synthesized. Selective hydrogenation of the carbonyl group in the acyl fragment and reduction of the conjugated double bond afforded in high yield the corresponding 3-alkyl(aralkyl) derivatives possessing either natural or modified prostaglandin -chain. Reduction of the conjugated double bond in vinylogous 3-alkyl(aralkyl)tetronic acid amides with sodium cyanotrihydridoborate gave a mixture of stereoisomeric -amino lactones which underwent retro-Michael elimination of the amine residue, leading to 3-alkyl(aralkyl)-2,5-dihydrofuran-2-ones. The latter can be regarded as synthons for 11-deoxy-10-oxaprostanoids.     

Synthesis and properties of 1,3-diaza-2-phospholo[4,5-d]pyrimidines

Reaction of 5-amino-4-alkyl(aryl or aralkyl)aminopyrimidines with PCl₅ gives 2,2-dichloro-3-alkyl(aryl or aralkyl)-1,3-diaza-2-phospholo[4,5-d]pyrimidines, which on treatment with piperidine or morpholine are converted into the corresponding 2,2-diamino derivatives. The latter, on boiling in water or aqueous alcohol, give the dipiperidides or dimorpholides of the corresponding 5-pyrimidylamidophosphoric acids.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 710–712, May, 1970.     

Total synthesis of thienamycin analogs. II Synthesis of 2-alkyl and 2-aryl thienamycin nuclei

A new general synthesis leading to 2-alkyl and 2-aryl-1-carba-2-penem-3-carboxylic acids involves the preparation of a key thiolester intermediate 3. This is reacted with Me₂CuLi or (C₆H₅)₂MgCuX to give the corresponding methyl or phenyl ketone which undergoes a Wittig reaction to give the desired penems, which can be deblocked photolytically or by hydrogenolysis to give acids with good antibacterial activity.     

4-hydroxy-2-quinolones. 22.* Synthesis and biological properties of 1-alkyl(aryl)-2-oxo-3-carbethoxy-4-hydroxyquinolines and their derivatives

The presently known method for obtaining ethyl esters of 1-alkyl(or aryl)-2-oxo-4-hydroxyquinoline-3-carboxylic acids and their derivatives has been improved. Results are presented from an investigation of the anticoagulant, analgesic, and antiinflamatory activities of the synthesized compounds.     

A one-step radical synthesis of pyrrol-2-acetic acids

Pyrrol-2-acetic acids were generated following a procedure involving I-transfer radical addition of iodoacetic acids to pyrrole with spontaneous loss of HI. This procedure also allows for efficient syntheses of 2-alkyl pyrroles through subsequent thermolytic decarboxylation.     

Directed synthesis and immunoactive properties of (2-hydroxyethyl)ammonium salts of 1-R-indol-3-ylsulfanyl(sulfonyl)alkanecarboxylic acids

A general method for the synthesis of 1-alkyl(allyl)(benzyl)-substituted (indol-3-yl)-sulfanylalkanecarboxylic acids and hexane-1,6-diyl(1,4-phenylenemethylene)bisindol-3-ylsulfanylalkanecarboxylic acids from the corresponding N-substituted indoles and bisindoles, thiourea, iodine, and halogencarboxylic acids was developed. The oxidation of substituted (indol-3-yl)sulfanylalkanecarboxylic acids for the first time afforded their analogs containing the sulfonyl group. New (2-hydroxyethyl)ammonium salts of 1-R-indol-3-ylsulfanyl(sulfonyl)-alkanecarboxylic acids, which are structural analogs of highly active immunomodulators of indacetamin and VILIM, were synthesized. Among the studied (2-hydroxyethyl)ammonium salts of 1-R-indol-3-ylsulfanylacetic and -sulfonylalkanecarboxylic acids, the compounds exhibiting high dose-dependent antiproliferative activity by the ability to affect the spontaneous and mitogen-stimulated splenocyte proliferation of mice in vitro were found.     

Synthesis of novel 1-phenyl-1H-indole-2-carboxylic Acids. I. Utilization of ullmann and dieckmann reactions for the preparation of 3-hydroxy, 3-alkoxy,and 3-alkyl derivatives

Methods for the synthesis of novel 3-hydroxy, 3-alkoxy, and 3-alkyl indole-2-carboxylic acids and esters are described. Dieckmann cyclization of various 2-[(carboxymethyl)amino]benzoic acid diesters yielded 1-unsubstituted-, 1-methyl-, and 1-phenyl-3-hydroxy-1H-indole-2-carboxylic acid esters. An Ullmann reaction with bromobenzene converted 1H-indoles to 1-phenylindoles.     

Features of reaction of substituted 4-oxobutanoic acids and 3<Emphasis Type="Italic">H</Emphasis>-furan-2-ones with 1,3-binucleophiles

Differences were found in reactions of 4-alkyl(aryl)-substituted 4-oxobutanoic acids and 3H-furan-2-ones with 1,3-binucleophiles, 2-(aminomethyl)aniline and 2-(aminophenyl)methanol. Depending on initial substrates different fused tricyclic systems are formed.     

Synthesis and structure of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahydropyrimidine-4-carboxylic acids

Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohydropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.     

Reaction of 3-Acetyl-4,6,6-trimethyl-5,6-dihydro-2-pyrone with Carboxylic Acid Hydrazides

The reaction of 3-acetyl-4,6,6-trimethyl-5,6-dihydro-2-pyrone with the hydrazides of a series of carboxylic acids led to the synthesis of 5-alkyl(cyanomethyl)carbonyl-3,5a,7,7-tetramethylpyrazolino-4,5-c]tetrahydro-2-pyrones, which are the products from cyclization of the intermediately formed alkyl(cyanomethyl)hydrazones of 3-acetyl-4,6,6-trimethyl-5,6-dihydro-2-pyran. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 998–1001, July, 2005.