Synthesis of 5,5′-Dialkyl-6,6′-dichloro-2, 2′-bipyridines

5,5′-Dialkyl-6,6′-dichloro-2,2′-bipyridines were synthesized starting from 3-substituted 2-chloro-6-iodopyridines using Pd-catalyzed coupling conditions. 6-Alkyl-3,5-dichloro-2H-1,4-oxazin-2-ones were excellent precursors for the synthesis of these functionalized 2-iodo-6-chloropyridines.     

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.     

Chiral enrichment of 2-amino-2′-hydroxy-1,1′-binaphthyl

A new synthetic procedure for the formation of 2-amino-2′-hydroxy-1,1′-binaphthyl, and a new purification procedure through the formation of Schiff bases, purification of the Schiff bases, and breakdown of the Schiff bases through amine exchange, are described. Through the new purification procedure, greater than 99% purity of the compound can be obtained easily and reliably. A set of procedures were examined to compare the efficiency and reliability to resolve 2-amino-2′-hydroxy-1,1′-binaphthyl into enantiomers. A new procedure was discovered to enrich enantiomeric excess from less than 10% to 95–99% in one step. Even a racemic mixture from an achiral procedure can be enriched to 67% e.e. in about 4% yield. The X-ray crystal structure of the racemic mixture [rhombohedral, space group Iba2, a=15.718(2) Å, b=21.703(2) Å, c=8.5398(9) Å, V=2913.2(5) ų, R1=0.0705, Z=8, d_calcd=1.301 g/cm³, F(000)=1200 e] was solved to elucidate the intriguing behavior of this compound.     

Calorimetric study of 2′-methylacetophenone and 4′-methylacetophenone

Values of the condensed phase standard (p = 0.1 MPa) molar enthalpy of formation for 2′- and 4′-methylacetophenones were derived from the standard molar energies of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry. The values of the standard molar enthalpy of vaporization, at T = 298.15 K, were measured by Calvet microcalorimetry. Combining these two values, the following enthalpies of formation in the gas phase, at T = 298.15 K, were then derived: 2′-methylacetophenone, –(115.7 ± 2.4) kJ · mol⁻¹, and 4′-methylacetophenone, –(122.6 ± 2.4) kJ · mol⁻¹. Substituent effects are discussed in terms of stability and compared with other similar compounds. The value of the standard molar enthalpy of formation for 3′-methylacetophenone was estimated from isomerization schemes.     

Preparation of DNA duplexes containing 2′-fluoro-2′-deoxyuridine and arabinosyluracil

The synthesis of two 14-membered duplexes containing 2-fluoro-2-deoxyuridine and 1--D-arabinosyluracil, respectively., has been effected by chemical ligation (CL). During the synthesis of the first of them, it was observed that the ammonolysis of the completely blocked ACGGAU^2F was accompanied by the transformation of the modified unit into arabinouridine with the formation of 45% of ACGGAU^ara. It has been established that the introduction of an electron-accepting substituent adjacent to the reacting 3-OH group has no influence on a characteristic feature established previously: CL is considerably more effective if the reacting phosphate group is present at the 3-end, and not the 5-end, of the oligonucleotide.M. V. Lomonosov Moscow State University. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 263–267, March–April, 1991.     

Synthesis of β-L-2′,3′-Dideoxy-2′-fluoro-3′-hydroxymethylarabinofuranosyl Pyrimidine Nucleosides

β-2′,3′-Dideoxy-2′-fluoro-3′-hydroxymethylarabinofuranosylthymine 10 and cytosine 12 were synthesized from L-xylose and were found to be inactive against HIV-1 in acutely infected lymphocytes.     

Synthesis of 2′-5′,3′-5′ linked triadenylates

2′-5′,3′-5′ Linked triadenylates have been synthesized by direct bisadenylylation of adenosine 2′ and 3′ hydroxyls with an adenosine 5′-phosphorochloridite followed by oxidation.     

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 Dioxacyclophanes Derived from 1,1′-Binaphthyl-2, 2′-diol

Abstract

The Williamson reaction between (R,S)-[1,1′-binaphthyl]-2, 2′-diol 1 and (R,S)-2,2′-bis (bromomethyl)-1,1′ binaphthyl 2 in acetone, gave the diastereoisomeric dioxacyclophanes (R?, S?)-3a and (R?, R?)-3b in high yield.     

An Efficient Preparation of 4, 4′-Dicarboxy-2, 2′-Bipyridine

A convenient and high yield preparation of 4, 4′-dicarboxy-2, 2′-bipyridine from the oxidation 4, 4′-dimethyl-2, 2′-bipyridine with potassium dichromate in sulfuric acid is reported.     

Resolution and determination of the absolute configuration of 3,3′4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxylic acid

(±)-3,3′4,4′-Tetramethyl-1,1′-diphosphaferrocene-2-carboxylic acid 1 was resolved via diastereomeric salts with brucine. The (R)-absolute configuration of (+)-1 was determined by X-ray crystallography.     

Synthesis of 2-O-ethyl analogues of 3′-azido- and 3′-fluoro-2′,3′-dideoxyuridines and evaluation of their biological activity against HIV

Summary 2-O-Ethyluracil and 2-O-ethylthymine were silylated with 1,1,1,3,3,3-hexamethyldisilazane and condensed in the presence ofTMS triflate with 2,3-dideoxy-3-fluoro-D-erythro-pentofuranoside, 3-azido-2,3-dideoxy-D-erythro-pentofuranoside, and 2,3-dideoxy-3-phthalimido--D-erythro-pentofuranose derivatives to give the corresponding 2-O-ethyl nucleosides. Deprotection with saturated methanolic ammonia afforded the 2,3-dideoxy-3-fluoro-2-O-ethyluridines, whereas 3-azido-2,3-dideoxy-3-O-ethyluridine was obtained by deprotection with tetrabutylammonium fluoride in tetrahydrofuran. 3-Amino-2,3-dideoxy-3-O-ethyluridine could be obtained only by treatment of the corresponding 3-azido nucleoside with triphenylphosphine in pyridine. 3-Deoxy-2-O-ethyl-3-fluorothymidine (6b) showed moderate activity against HIV-1.

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Synthese von 2-O-Ethyl-Analogen von 3-Azido- und 3-Fluor-23-dideoxyuridinen und Bestimmung ihrer biologischen Aktivität gegenüber HIV

Zusammenfassung 2-O-Ethyluracil und 2-O-Ethylthymin wurden mit 1,1,1,3,3,3-Hexamethyldisilazan silyliert und in Gegenwart vonTMS-triflat mit 2,3-Dideoxy-3-fluoro-D-erythro-pentofuranosid, 3-Azido-2,3-dideoxy-D-erythro-pentofuranosid und 2,3-Dideoxy-3-phthalimido--D-erythro-pentofuranosederivaten zu den entsprechenden 2-O-Ethyl-Nucleosiden umgesetzt. Entfernung der Schutzgruppe mit gesättigter methanolischer Ammoniaklösung lieferte 2,3-Dideoxy-3-fluor-2-O-ethyluridin; 3-Azido-2,3-dideoxy-3-O-ethyl-uridin wurde durch Entschützung mit Tetrabutylammoniumfluorid in Tetrahydrofuran erhalten. 3-Amino-2,3-dideoxy-3-O-ethyl-uridin konnte nur durch Behandeln des entsprechenden 3-Azido-Nucleosids mit Triphenylphosphin in Pyridin hergestellt werden. 3-Deoxy-2-O-ethyl-3-fluor-thymidin (6b) zeigt geringe Aktivität gegenüber HIV-1.

     

Diastereoselective and enantioselective synthesis of 4′-aza analogues of 2′,3′-dideoxynucleosides

A diastereo- and enantioselective synthesis of 4′-aza analogues of 2′,3′-dideoxynucleosides has been designed by the strategy of the 1,3-dipolar cycloaddition reaction of a Vasella-type nitrone. The reaction leads to (1′R)- and (1′S)-4′-aza analogues of 2′,3′-dideoxythimidine and fluorouridine, in enantiomerically pure forms.     

Synthesis of 5′-benzoyl-2′-hydroxychalcones and related flavonoid compounds

Summary 5 -Benzoyl-2 -hydroxychalcones were synthesized by the condensation of 5 -benzoyl-2 -hydroxyacetophenone with aromatic aldehydes in presence of an ethanolic solution of potassium hydroxide. Derivatives of 6-benzoylflavonoids were prepared from chalcones.     

New route for the synthesis of 2-thiouracil analogues of 3′-azido-2′,3′-dideoxy nucleosides

Summary Reaction of 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pentofuranoside (5) with silylated 2-thiouracil and 5-alkoxy-2-thiouracils in the presence of trimethylsilyl trifluoromethanesulfonate afforded an anomeric mixture of the corresponding 3-azido-2,3-dideoxy-2-thiouridine derivatives with the -anomer as the main product. Deprotected nucleosides were obtained by treatment with tetrabutylammonium fluoride.

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Ein neuer Weg zur Synthese von 2-Thiouracil-Analogen von 3-Azido-2,3-dideoxy-Nucleosiden

Zusammenfassung Die Reaktion von 3-Azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pentofuranosid (5) mit silyliertem 2-Thiouracil und 5-Alkoxy-2-thiouracil in Gegenwart von Trimethylsilyltrifluormethansulfonat ergab eine anomere Mischung der entsprechenden 3-Azido-2,3-dideoxy-2-thiouridin-Derivate, wobei das -Anomer das Hauptprodukt darstellte. Die ungeschützten Nucleoside wurden mittels Behandlung mit Tetrabutylammoniumfluorid erhalten.

     

Cyclization of 2′-Aminochalcones with Chlorosulfonyl Isocyanate

Cyclization of 2′-aminochalcones 1a-e with chlorosulfonyl isocyanate (CSI), at low temperature, afforded 2(1H)-quinazolinone 2a-e and 1H-2,1,3-benzothiadiazine 2,2-dioxide 3a-e derivatives.     

Photolysis of adamantane-2-spiru-3′-diazirine

The spectral characteristics and photochemical transformations of adamantane-2-spiro-3-diazirine and its 5-hydroxy derivative were studied. The transformations of the photoexcited molecules of adamantane-2-spiro-3-diazirine in individual solvents and their mixtures and with various sources of UV radiation were studied by gas-liquid chromatography. The main process in saturated hydrocarbons is the formation of diazoadamantane, which is then converted into adamantanone azine. The addition of small amounts of formic or acetic acid leads to the formation of significant amounts of alkyladamantanes, which are the products from transformations of the intermediately formed carbene adamantylidene. Concurrent transformation paths are also observed in cyclohexene. It is suggested that the adamantylidene is preceded by the formation of an exciplex of diazirine with the polar solvent molecule. The ambiphilic nature of adamantylidene in the photolysis of diazirines was demonstrated by concurrent carbenylation.Kiev Polytechnical Institute, L. V. Pisarzhevskii Institute of Physical Chemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Higher Chemical Technology School, Prague. Translated from Teoreticheskaya i Ésperimental'naya Khimiya, Vol. 27, No. 2, pp. 211–220, March–April, 1991. Original article submitted July 11, 1989.     

Thermal analysis of 5′-deoxy-5′-iodo-2′,3′-O-isopropylidene-5-fluorouridine

The melting temperature, melting enthalpy, and specific heat capacities (C _p) of 5′-deoxy-5′-iodo-2′,3′-O-isopropylidene-5-fluorouridine (DIOIPF) were measured using DSC-60 Differential Scanning Calorimetry. The melting temperature and melting enthalpy were obtained to be 453.80 K and 33.22 J g^?1, respectively. The relationship between the specific heat capacity and temperature was obtained to be C _p/J g^?1 K^?1 = 2.0261 – 0.0096T + 2 × 10^?5 T ² at the temperature range from 320.15 to 430.15 K. The thermal decomposition process was studied by the TG–DTA analyzer. The results showed that the thermal decomposition temperature of DIOIPF was above 487.84 K, and the decomposition process can be divided into three stages: the first stage is the decomposition of impurities, the mass loss in the second stage may be the sublimation of iodine and thermal decomposition process of the side-group C₄H₂O₂N₂F, and the third stage may be the thermal decomposition process of both the groups –CH₃ and –CH₂OCH₂–. The obtained thermodynamic basic data are helpful for exploiting new synthetic method, engineering design, and commercial process of DIOIPF.     

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.