Diels-alder reactions with cyclic sulfones: VIII. Organic catalysis in the synthesis of spiro[1-benzothiophene-4,5′-pyrimidine]-2′,4′,6′-trione 1,1-dioxides and 2′-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-dioxides

5-Isopropenyl-2,3-dihydrothiophene 1,1-dioxide reacted with 5-methylidenepyrimidine-2,4,6-triones and 5-methylidene-2-thioxopyrimidine-4,6-diones in the presence of chiral amines or amino acids with high regio- and stereoselectivity to give optically active derivatives of barbituric and thiobarbituric acids spirofused at the 5-position to 1-benzothiophene 1,1-dioxide fragment. The reaction of 5-isopropenyl-2,3-dihydrothiophene 1,1-dioxide with 5-(2-methoxybenzylidene)-2-thioxopyrimidine-4,6-dione (generated in situ from 2-methoxybenzaldehyde and thiobarbituric acid) in the presence of (?)-ephedrine or L-4-(tert-butyldimethylsiloxy) proline gave the corresponding 2-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-dioxide with an enantiomeric excess of 80%.     

Mechanism of Formation of Ribonucleoside Cyclic 2′,3′-Phosphates in the Reaction of Appropriate 3′,5′-Phos-Phorothioates with Epoxides

Abstract

It has been recently demonstrated in our laboratory CD that ribonucleoside cyclic 3′,5′-phosphorothioates react with epoxides to give as a major product corresponding cyclic 5′,3′-phosphates, We now report the results OF our ste-reochemical studies OF this reaction. WE have Found that the diastereomerically pure (Sp) 3′.5′-CUFLPS when treated with styrene [¹⁰O]-oxide in ethanol gives the same isotopomer OF 2′,3′-[¹⁰O]cUMP as that obtained From the reaction of endo-2′.3′-cUMPS with styrene [¹⁰O]-oxide. This result strongly supports our previous assumption that reaction of 3′,5′-cNMPS with epoxides proceeds via 3′-oxathiaphosphorylated intermediate (L) which is Formed with inversion and decomposes to 2′,3′-cNMP with retention of configuration at phosphorus atom.     

Copper(II) complexing with 2′,2′-diethylheptanohydrazide

Acid-base properties of 2′,2′-diethylheptanohydrazide (DEHH) and its complex formation with copper(II) ions in water-isopropanol solutions were studied. Cationic complexes with [Cu²⁺] : [DEHH] ratios of 1 : 1 and 1 : 2 were found to be formed in weak acid media, and an uncharged complex with a [Cu²⁺] : [DEHH] ratio of 1 : 2 was found to be formed in a basic medium. log K _st values were determined. The data obtained were compared with the stability constants of copper(II) 2′,2′-diethylbenzohydrazide complexes.     

Reaction of 2-pyridyllithium with azine N-oxides. Simple and convenient method for the synthesis of 2,2′-bipyridine 1-oxide and 2,2′:6′,2″:6″2′″-tetrapyridine 1′-oxide

In the reaction of 2-pyridyllithium with quinoline 1-oxide and isoquinoline 2-oxide a nucleophilic substitution of hydrogen occurs to form the corresponding pyridin-2-ylquinolines. A dimerization of the substrate occurs with pyridine 1-oxide, 2,2′-bipyridine 1-oxide or quinoxaline N-oxide. A similar dimerization in good yield occurs when treating azine N-oxides with tert-butyllithium and this serves as a simple and convenient method for preparing bi- and tetrapyridines. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 223–229, February, 2009.     

Investigations in the region of 2,3′-biquinoline. 3. Synthesis of 2′-alkyl(aryl)-1′,2′-dihydro-2,3′-biquinolines and 2′-alkyl(aryl)-2,3′-biquinolines

A method was developed for the synthesis of 2-alkyl(aryl)-1,2-dihydro-2,3-biquinolines, based on the addition of organolithium compounds to 2,3-biquinoline in the presence of tetramethylethylenediamine. Their oxidation with manganese dioxide led to 2-alkyl(aryl)-2,3-biquinolines.For Communication 2, see [1].Stavropol State University, Stavropol 355009, Russia. Russian Chemical-Technology University, Moscow 125190. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 350–354, March, 1998.     

Investigations of 2,3′-biquinolyl. 9. Reaction of 1′,4′-dihydro-2,3′-biquinolyl with organolithium compounds

The 1,4-dihydro-2,3-biquinolyl reacts with organolithium compounds to form the mixture of 4-R-1,4-dihydro-2,3-biquinolyls and 2-R-1,2-dihydro-2,3-biquinolyls in the ratio analogous to the conversion in the series of 2,3-biquinolyl. The utilization of the complex, the organolithium compound-TMEDA, in this process leads, after treatment of the reaction mixture with water, exclusively to 2-R-1,2-dihydro-2,3-biquinolyls. Treatment with methyl iodide leads to 1-methyl-2-R-1,2-dihydro-2,3-biquinolyls.     

Enantioselective imine Michael reaction for the preparation of the (8′R,8a′S)-8,8a′-dimethyl-1′,3′,4′,7′,8′,8a′-hexahydrospiro[1,3-dioxolane-2,2′(6′H)naphthalen]-6′-one building block. A formal synthesis of (+)-valencenol

The enantioselective Michael addition of a chiral imine of 4-protected 2-methylcyclohexane-1,4-dione to phenyl crotonate led after cyclization to the corresponding bicyclic lactam. Reductive cleavage of the chiral moiety followed by saponification gave the corresponding keto-acid, which was cyclized to afford a lactone. Belleau–Fujimoto reaction of the lactone then led to the title building block (diastereoselectivity 96:4, e.e. >98%) in 11% overall yield from the starting dione. (8R,8aS)-(+)-8,8a-Dimethyl-3,4,6,7,8,8a-hexahydronaphthalen-2(1H)-one was obtained after reduction of the carbonyl group, acetylation, and reductive cleavage–deprotection (52% overall yield), representing a formal synthesis of (+)-valencenol.     

Synthesis and mesomorphic properties of 4-methoxyphenyl 4′- n -alkoxy-2′,3′,5′,6′-tetrafluorobiphenyl-1-carboxylates

A novel type of 4-methoxyphenyl 4′-n-alkoxy-2′,3′,5′,6′-tetrafluorobiphenyl-1-carboxylates have been synthesized. Textural observations by polarizing microscopy and DSC measurements of the phase transitions show that all of these compounds are thermotropic liquid crystals with only a nematic mesophase. The relationship between the properties and chemical structures of these compounds is discussed.     

Selective formation of thecis isomer of the nitridotechnetium(V) complex with 2,2′:6′,2″-terpyridine

The reaction of [TcNCl₂(PPh₃)₂] with 2,2′:6′,2″-terpyridine producedcis-[TcNCl₂(terpy)] selectively. The resulting complexes were characterized by¹H NMR and IR spectroscopy. The geometries of thecis andtrans isomers were estimated by theoretical calculations following a density functional method. Thecis isomer is likely more stable than thetrans one with respect to thetrans influence of the nitrido ligand. Furthermore, the behavior of nitridotechnetium complexes in polar solvents was compared to Os-analogues.     

Synthesis of Novel 1-Arylsulfonyl-4-(1′-N-2′, 3′, 4′, 6′-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazides

Some 1-arylsulfonylthiosemicarbazides have been reported as fungicides1 and bacterio-static agents2. Recently, it is well documented that thiosemicarbazide is a novel class ofnon-peptide antagonists for bradykinin B2 , which is beneficial in the symptomat…     

Synthesis of 2′,3′-Dideoxy-2′-Fluorokanamycin A

2′,3′-Dideoxy-2′-fluorokanamycin A (23) was prepared by condensation of 6-azido-4-0-benzoyl-2,3,6-trideoxy-2-fluoro-α-D-ribo-hexopyranosyl bromide (13) and a protected disaccharide (19). Methyl 4,6-0-benzylidene-3-deoxy-β-D-arabino-hexopyranoside (5) prepared from methyl 4,6-0-benzylidene-3-chloro-3-deoxy-β-D-allo-hexopyranoside (1) by oxidation with pyridinium chlorochromate followed by reduction with Na₂ S₂O₄ was fluorinated with the DAST reagent to give methyl 4,6-O-benzylidene-2,3-dideoxy-2-fluoro-β-D-ribo-hexopyranoside (7). Successive treatment of 7 with NBS, NaN₃ and SOBr₂ gave 13. The structure of the final product (23) was determined by the ¹H and ¹⁹F and shift-correlated 2D NMR spectra.     

Amperometric Immunosensor for the Determination of 2′,3′-dideoxyinosine

Abstract

An amperometric immunosensor, based on carbon paste impregnated with solubilized antidideoxyinosine (from rabbit lyophilized powder, whole antiserum) has been constructed for the assay of anti-HIV agent dideoxyinosine (didanosine, DDI). The amperometric immunosensor was reliably used for dideoxyinosine assay in the 900 pmol/L to 9 nmol/L concentration range, with a detection limit of 180 pmol/L, at E = +1.04 V vs. Ag/AgCl. The construction of the immunosensor is reproducible. Its surface can be easily renewed by simple polishing on an aluminium paper. The new amperometric immunosensor is reliable for the assay of 2′,3′-dideoxyinosine in raw material as well as in its pharmaceutical formulation (Videx tablets).     

Developments in the Dehydrogenative Electrochemical Synthesis of 3,3′,5,5′-Tetramethyl-2,2′-biphenol

The symmetric biphenol 3,3′,5,5′-tetramethyl-2,2′-biphenol is a well-known ligand building block and is used in transition-metal catalysis. In the literature, there are several synthetic routes for the preparation of this exceptional molecule. Herein, the focus is on the sustainable electrochemical synthesis of 3,3′,5,5′-tetramethyl-2,2′-biphenol. A brief overview of the developmental history of this inconspicuous molecule, which is of great interest for technical applications, but has many challenges for its synthesis, is provided. The electro-organic method is a powerful, sustainable, and efficient alternative to conventional synthesis to obtain this symmetric biphenol up to the kilogram scale. Another section of this article is devoted to different process management strategies in batch-type and flow electrolysis and their respective advantages.     

Synthesis of Steroidal Spiro-1′,2′,4′-triazolidine-3′-thiones

Steroidal ketone thiosemicarbazones (4–6), obtained from the corresponding ketones(1–3), on oxidative cyclization with H₂O₂ at 0°C provide title compounds (7–9), respectively. The structures of these compounds have been established on the basis of their elemental analytical and spectral data.     

Synthesis of 2′-deoxy-2′-fluororibo- and 2′-deoxy-2′,2′-difluororibonucleosides derived from 6-(het)aryl-7-deazapurines

A series of novel sugar-modified derivatives of cytostatic 6-hetaryl-7-deazapurine ribonucleosides (2′-deoxy-2′-fluororibo- and 2′-deoxy-2′,2-difluororibonucleosides) bearing an aryl or hetaryl group in position 6, was prepared and screened for biological activity. The fluororibo derivatives were prepared by aqueous palladium catalyzed cross-coupling reactions of the corresponding 6-chloro-7-deazapurine 2′-deoxy-2′-fluororibonucleoside 11 with (het)arylboronic acids. The key intermediate 11 was prepared by a six-step sequence from the corresponding arabinonucleoside by selective protection of 3′- and 5′-hydroxyls by acid-labile groups followed by stereoselective S_N2 fluorination and deprotection. The difluororibo-series was prepared by non-stereoselective glycosidation of 6-chloro-7-deazapurine with benzoyl-protected 2-deoxy-2,2-difluoro-d-erythro-pentofuranosyl-1-mesylate followed by cross-couplings, separation of anomers and deprotection. The title nucleosides did not show considerable cytostatic or antiviral activity.     

Synthesis of New 2′-(2- and 3-Aminopropanoyl)-6′,7′-dimethoxy-2′,3′-dihydro-1′H-spiro[cyclopentane-1,4′-isoquinoline]-1′-carboxamides

Russian Journal of Organic Chemistry - 6′,7′-Dimethoxy-N-methyl-2′,3′-dihydro-1′H-spiro[cyclopentane-1,4′-isoquinoline]-1′-carboxamide reacted with...     

On the influence of the chiral side linking bridge type upon the synclinic vs. anticlinic balance in the case of 2′,3′-difluoroterphenyl derivatives

A homologous series of new ferro- and antiferroelectric liquid crystals, containing 2′,3′-difluorosubstituted terphenyl core as a mesogenic core, has been recently synthesised. Synthetic routes and mesomorphic properties were described. Liquid crystal phases were preliminarily determined by thermomicroscopic and microcalorimetric measurements and verified by dielectric measurements and miscibility methods. Temperatures and enthalpies of phase transitions are given.     

Reactions of 2′-oxo-1′,2′-dihydrospiro[cyclopropane-1,3′-indole]-2,2,3,3-tetracarbonitriles with nucleophiles

2′-Oxo-1′,2′-dihydrospiro[cyclopropane-1,3′-indole]-2,2,3,3-tetracarbonitriles reacted with oxygencentered nucleophiles to form addition products at the cyano groups with conservation of the three-membered ring. Reactions of the title compounds with alcohols required the presence of base catalyst, and the products, 2-amino-4,4-dialkoxy-2′-oxo-1′,2′-dihydrospiro[3-azabicyclo[3.1.0]hex-2-ene-6,3′-indole]-1,5-dicarbonitriles, were converted into the corresponding 2-imino-2′,4-dioxospiro[3-azabicyclo[3.1.0]hexane-6,3′-indole]-1,5-dicarbonitriles and 2,2′,4-trioxospiro[3-azabicyclo[3.1.0]hexane-6,3′-indole]-1,5-dicarbonitriles by the action of acetic and sulfuric acids, respectively. The reactions with ketone oximes occurred in the absence of a catalyst, yielding 2-amino-4,4-bis(alkylideneaminooxy)-2′-oxo-1′,2′-dihydrospiro[3-azabicyclo[3.1.0]hex-2-ene-6,3′-indole]-1,5-dicarbonitriles. The reactions with thiols, aliphatic amines, and anilines were accompanied by opening of the three-membered ring. In the reactions with triphenylphosphine and thiols 2-(2-oxo-2,3-dihydro-1H-indol-3-ylidene)malononitrile was obtained, while morpholine and N,N-dimethylaniline gave rise, respectively, to 3,3-diaryl-and 3,3-dimorpholino-1H-indol-2(3H)-ones and tri- and dicyanoethylene derivatives.     

2′,6′-Dimethoxyflavone as an Aid to the Crystallization of Benzoic Acids and X-Ray Structure of the Inclusion Compound with 2,4,6-Trimethoxybenzoic Acid

The crystal structure of the inclusion compound formed between 2-6-dimethoxyflavone and 2,4,6-trimethoxybenzoic acid has been investigated by single-crystal X-ray analysis. The compound crystallizes in the triclinic system, space group P-1, as do inclusion compounds with acetic, propionic, and bromoacetic acids. However, the larger 2,4,6-trimethoxybenzoic acid molecule induces a layered structure.