Nucléosides de synthèse XXI. Obtention spécifique de ribonucléosides de configuration anomérique α

A new and stereospecific synthesis of a chemical precursor of α-D-ribonucleosides, namely, 1-α-D-ribofuranosyl-4-carboxamido-5-aminoimidazole ( 1 ) is described using 2-thio-α-D-ribofurano[1,2-d]-oxazolidine as the starting material.     

Introduction of a New Class of Ligands for the Metal-Catalyzed Enantioselective Synthesis

Protected thiosugars were prepared as ligands for the metal-catalyzed enantioselective synthesis. The protecting groups in these ligands were varied to test a proposed new concept for the metal-catalyzed enantioselective synthesis. This new concept centres on the use of a stair-like ligand with a large substituent on one side and a small substitutent on the other rather than the commonly employed ligands which have C₂ symmetry (see Fig.3). In such a ligand, both substituents should have a major influence on the coordination of a prochiral substrate. To test this proposal, 3-thio-α-D -glucofuranose derivatives with the following substituents were synthesized: 1,2-O-isopropylidene-5,6-O-methylidene (see 24 ), 1,2:5,6-di-O-isopropylidene (see 2 ), 5,6-O-cyclohexylidene-1,2-O-isopropylidene (see 23 ), 1,2-O-cyclohexylidene-5,6-O-isopropylidene (see 14 ), 1,2:5,6-di-O-cyclohexylidene (see 13 ), 5,6-O-(adamantan-2-ylidene)-1,2-O-isopropylidene (see 21 ), and 1,2:5,6-di-O-(adamantan-2-ylidene) (see 25 , Table 2). As a representative of the allofuranoses, 1,2:5,6-di-O-isopropylidene-3-thio-α-D -allofuranose ( 6 ) was chosen. The following derivatives of 1,2-O-isopropylidene-α-D -xylofuranose were also synthesized: 1,2-O-isopropylidene-5-deoxy-3-thio-α-D -xylofuranose ( 29 ), 1,2-O-isopropylidene-3-thio-α-D -xylofuranose ( 28 ) and 5-O-[(tert-butyl)-diphenylsilyl]-1,2-O-isopropylidene-3-thio-α-D -xylofuranose ( 15 , see Table 2). The proposed concept was tested using the copper-catalyzed 1,4-addition of BuMgCl to cyclohex-2-en-1-one. The enantioselectivity was very dependent on the ligand used and was up to 58%.     

Polycarbonyl heterocycles. Part III. Synthesis of 2,3-furanodione derivatives by ring transformations of thiazolidine-4,5-dione derivatives

The base catalyzed isomerization of 2-(aroyl-methylene)-3-aryl-thiazolidine-4,5-dione derivatives1 leads to salts of 1-aryl-3-aroyl-4-hydroxy-pyrroline-2-thio-5-one and aliphatic amines2. It was found that2 undergo further transformation to 4-thioanilido-5-arylo-2,3-furanodione derivatives4. This series of reaction provides a convenient synthetic route to 2,3-furanodione derivatives4.

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Polycarbonyl-Heterocyclen, 3. Mitt.: Synthese von 2,3-Furandion-Derivaten durch Ringtransformation von Thiazolidin-4,5-dion-Derivaten

Zusammenfassung Die basenkatalysierte Isomerisierung von 2-(Aroylmethylen)-3-aryl-thiazolidin-4,5-dionen1 führt zu Salzen von 1-Aryl-3-aroyl-4-hydroxy-pyrrolin-2-thio-5-on und aliphatischen Aminen2. Die letzteren gehen in 4-Thioanilido-5-arylo-2,3-furandion-Derivate4 über. Diese Reaktionsfolge stellte eine vorteilhafte synthetische Route zu 2,3-Furandionen dar.

     

Thioglycosides as Potential Glycosyl Donors in Electrochemical Glycosylation Reactions. Part 2: Their Reactivity Toward Sugar Alcohols.

Abstract

Constant potential electrolysis of the glycosyl donors p-methylphenyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside (1) and p-methylphenyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (4) in dry acetonitrile in the presence of various primary and secondary sugar alcohols, performed in an undivided cell, gave β-linked disaccharide derivatives selectively in good yields. Oxidative coupling of p-methoxyphenyl 2,3,4-tri-O-benzyl-1-thio-β-L-fucopyranoside (2 1) with p-methoxybenzyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside (16) gave selectively the α-linked disaccharide 22 in good yield.     

Selective Protecting Method for the Individual Hydroxyl Groups of Kdn

ABSTRACT

Selective protection for the individual hydroxyl groups of methyl (phenyl 3-deoxy-2-thio-β-D-glycero-D-galacto-2-nonulopyranosid)onate (2) was examined. The 4-, 5-, and 7-hydroxyl groups of methyl (phenyl 3-deoxy-8,9-O-isopropylidene-2-thio-β-D-glycero-D-galacto-2-nonulopyranosid)onate (3) were found selectively to be protected by t-butyldimethylsilyl, methoxymethyl, and benzoyl groups, respectively. In order to obtain the 8- and 9-hydroxyl derivatives selectively, methyl (phenyl 4,5,7-tri-O-acetyl-9-O-t-butyldimethylsilyl-3-deoxy-2-thio-β-D-glycero-D-galacto-2-nonulopyranosid)onate (12) and methyl (phenyl 4,5,7,8-tetra-O-benzyl-9-O-triphenylmethyl-3-deoxy-2-thio-β-D-glycero-D-galacto-2-nonulopyranosid)onate (19) were prepared in moderate yields.     

LARGE SCALE SYNTHESIS OF 2-AZIDODEOXY GLUCOSYL DONORS

Starting from readily available phenyl 1-thio-β-D-mannopyranoside, phenyl 2-azido-2-deoxy-1-thio-β-D-glucopyranoside (9) was synthesized on multigram scale using inexpensive reagents.     

Preparation and lectin binding specificity of polystyrene particles grafted with glycopolymers bearing S-linked carbohydrates

Polystyrene particles bearing ATRP initiating groups, obtained by emulsifier-free emulsion polymerization of styrene (St) and 2-chloropropyloxyethyl methacrylate (CPEM), were subjected to surface-initiated activator generated by electron transfer for atom transfer radical polymerization (AGET ATRP) using glycomonomers, i.e., 4-vinylbenzenesulfonamidoethyl 1-thio-β-d-glucopyranoside (1) and 4-vinylbenzenesulfonamidoethyl 1-thio-β-d-lactoside (2). The glycopolymer-grafted polystyrene particles obtained Gp1 and Gp2 were shown to have hydrated graft layers of 15–65 nm in thickness on the cores of 370 nm in diameter. Gp1 and Gp2 coagulated in the presence of concanavalin A (Con A) and that of peanut agglutinin (PNA), respectively, showing highly specific response toward lectins.     

Reaction of chloroacetylenephosphonates with 5-thiotetrazoles

1-Chloroacetylene-2-phosphonates react with 1-substituted 5-thio-1H-1,2,3,4-tetrazoles in anhydrous acetonitrile to form new fused heterocycles, 6-(dialkoxyphosphoryl)-3H-[1,3]thiazolo[3,2-d][1,2,3,4]tetrazol-7-ium chlorides, with a small quantity of Z-dialkyl (1,2-bis{[1-amino(methyl/phenyl)-1H-tetrazol-5-yl]sulfanyl}ethenyl)phosphonates.     

SYNTHESIS OF 1,3-THIAZANE-2,4-DIONE AND 2-THIO-5,6-DIHYDROURACIL AND THEIR DERIVATIVES

Abstract

1,3-Thiazane-2,4-diones and 2-thio-5,6-dihydrouracils belong to biologically interesting groups of compounds. The 5-ethyl-6-phenyl derivative (Dolitrone) of the former has shown marked activity as an intravenous general anaesthetic. Several derivatives of 2-thio-5,6-dihydrouracil have been reported to possess antitubercular and antithyroid activity. In the present study these two groups of compounds have been synthesised from common starting materials, namely, different α,β-unsaturated acids and thiourea.     

Studies on the Thioglycosides of N-Acetyl-Neuraminic Acid 8: Synthesis of S-(α-Sialyl)-(2→ 6)-β-Hexopyranosyl and -(2→ 6')-β-Lactosyl Ceramides Containing β-Thioglycosidically Linked Ceramide

ABSTRACT

Coupling of the sodium salt of S-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-galacto-2-nonulopyranosylonate)-(2→'6)-2,3,4-tri-O-acetyl-1,6-dithio-β-D-glucopyranose (5), -β-D-galactopyranose (8), or S-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→'6)-O-(2,3,4-tri-O-acetyl-6-thio-β-D-galactopyranosyl)-(1→'4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranose (12), which were prepared from the corresponding 1-hydroxy compounds, 1, 2, and 9, via 1-chlorination, displacement with thioacetyl group, and S-deacetylation, with (2S,3R,4E)-2-azido-3-O-benzoyl-1-O-(p-toluenesulfonyl)-4-octadecene-1,3-diol (13), gave the corresponding β-thioglycosides 14, 18 and 22, respectively in good yields. The β-thioglycosides obtained were converted, via selective reduction of the azide group, condensation with octadecanoic acid, and removal of the protecting groups, into the title compounds.     

Mono-Triflation of Carbohydrate Diols and Triols

ABSTRACT

For five carbohydrate substrates [methyl 4,6-O-(phenylmethylene)-1-thio-α-D-glucopyranoside 1a, 1-cyano-1-deoxy-4,6-O-(phenylmethylene)-α-D-galactopyranose 2a, methyl α-D-xylopyranoside 3a, methyl β-D-arabinopyranoside 4a, and methyl 5-O-(tert-butyldiphenylsilyl)-α-D-ribofuranoside 5a], selective mono-triflation was achieved where the reacting hydroxyl is cis and vicinal to a heteroatom.     

Supramolecular networks constructed from mono- and bi-nuclear lanthanide complexes with 1,2-phenylenedioxydiacetic acid

[Tb₂(1,2-pdoa)₃ · 6H₂O] · H₂O (1) and [La(1,2-pdoa)(1,2-H₂pdoa)(OH) · H₂O] · 5H₂O (2) (1,2-H₂pdoa = 1,2-phenylenedioxydiacetic acid) have been synthesized and structurally characterized by single crystal X-ray diffraction. Complex 1 is a binuclear molecule in which one 1,2-pdoa ligand is a tetradentate bridge linking two Tb³⁺ ions, the other two 1,2-pdoa ligands bond Tb1³⁺ and Tb1A³⁺ via tetradentate chelating coordination. Tb³⁺ is nine-coordinate by six oxygens of 1,2-pdoa and three waters. Complex 2 is mono-nuclear with La³⁺ ten-coordinate by eight oxygens of two 1,2-pdoa, one hydroxide and one water. 1,2-Pdoa is tetradentate chelating with La³⁺ ion. The packing diagrams of 1 and 2 show supramolecular networks via H-bonds. The fluorescence spectrum of 1 shows characteristic emission of Tb³⁺ with ⁵D₄ → ⁷F_j (j = 6–3) transitions.     

Synthesis of α-D-Glucopyranosyl-(1-3)-α-D-Mannopyranosyl-(1-7)-4-Methylumbelliferone,A Fluorogenic Substrate for Endo-α-1,2-Mannosidase

ABSTRACT

α-D-Glucopyranosyl-(1-3)-α-D-mannopyranosyl-(1-7)-4-methylumbelliferone (Glc-Man-Muf) was synthesized as a potential fluorogenic substrate for endo-α-1,2-mannosidase. The synthesis was designed in a convergent way. The glucose donor ethyl 2,3,4,6-tetra-O-benzyl-1-thio-β-glucopyranoside and the mannose acceptor 1,2:4,6-di-O-isopropylidene-ß-D-mannopyranose were coupled in the presence of N-iodosuccinimide and trifluoromethane-sulfonic acid to yield the corresponding disaccharide derivative. After conversion into peracetylated α-D-glucopyranosyl-(1-3)-α-D-mannopyranose the disaccharide was attached to 4-methylumbelliferone using the Helferich method. After separation of the desired isomer, deacetylation yielded the title compound. Glc-Man-Muf was used as a substrate in endomannosidase assays with rat liver Golgi preparations as an enzyme source (in the presence of the α-glucosidase inhibitor deoxynojirimycin). The degradation of Glc-Man-Muf was linear with protein up to 300 μg and with time up to 2 h. V_max and K_m were determined to be 0.17 nmol/mg x h and 3.7 mM, respectively.     

Synthetic Studies on Sialoglycoconjugates 54: Synthesis of I-Active Ganglioside Analog

Abstract

A stereocontrolled synthesis of I-active ganglioside analog is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-O-benzyl-4,6-O-benzylidene-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (5) with methyl 4-O-acetyl-1,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (10) by use of N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) gave the desired trisaccharide 11, which was transformed into trisaccharide acceptor 14 via removal of the phthaloyl group followed by N-acetylation, and debenzylidenation. Glycosylation of 14 with methyl 3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (8) gave the biantennary compound 15, which was transformed into the acceptor 16. Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 16 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (17) afforded the desired hexasaccharide 19. Coupling of the hexasaccharide acceptor 20, prepared from 19 by reductive ring-opening of benzylidene acetal, with 17 gave octasaccharide derivative 21. Compound 21 was transformed, via removal of the benzyl group followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the final glycosyl donor 24. Condensation of 24 with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18) gave the β-glycoside 25, which on channeling through selective reduction of azido group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title compound 28.     

Expeditious Synthesis of a Trisubstrate Analogue for α(1→3)Fucosyltransferase

Abstract

The synthesis of cyclohexyl 2-acetamido-2-deoxy-3-O-{2-O-[2-(guanosine 5′-O-phosphate)ethyl]-α-L-fucopyranosyl}-β-D-glucopyranoside (1), a potential inhibitor of α(1→3)fucosyltransferases, is described. Target compound 1 was assembled via fucosylation of cyclohexyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside (6) with ethyl 2-O-[2-(benzoylhydroxy)ethyl]-3,4-O-isopropylidene-1-thio-β-L-fucopyranoside (5) followed by debenzoylation, subsequent condensation of the resulting compound with 3′,4′ -di-O-benzoyl-5′ -O-(2-cyanoethyl-N,N-diisopropylphosphoramidite)-2-N-diphenylacetylguanosine (10) and deprotection.     

Reaction of 1,2-diarylhydrazines with acetic anhydride catalyzed by 4-(dimethylamino)pyridine

Summary A new method for the synthesis of 1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-ones3 and 4-acetyl-1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-ones5 is presented. The reaction of 4,4-disubstituted 1,2-diarylhydrazines1 with acetic anhydride in the presence of an equimolar amount of 4-(dimethylamino)pyridine leads to mixtures of the corresponding acetyl derivatives2 and3. Under the same conditions, 2,2-disubstituted 1,2-diarylhydrazines yield mixtures of3 and5.

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4-(Dimethylamino)pyridin-katalysierte Reaktion von 1,2-Diarylhydrazinen mit Essigsäureanhydrid

Zusammenfassung Eine neue Methode zur Synthese von 1,2-Diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-onen3 und 4-Acetyl-1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-onen5 wird beschrieben. Die Reaktion von 4,4-disubstituierten 1,2-Diaryl-hydrazinen1 mit Essigsäureanhydrid führt in Gegenwart eines Äquivalentes 4-(Dimethylamino)pyridin zu Gemischen der entsprechenden Acetylderivate2 und3. Unter den gleichen Bedingungen werden aus 2,2-disubstituierten 1,2-Diarylhydrazinen Gemische aus3 und5 erhalten.

     

Preparation of Some Glycosyl Amino Acid Building Blocks via Click Reaction and Construction of a Glycotetrapeptide Library Using Spot Synthesis

The copper-catalyzed 1,3-dipolar cycloaddition reaction between ethyl 2,3,4-tri-O-actetyl-6-azido-6-deoxy-1-thio-β -d-glucopyranoside (2), ethyl 2,3,4-tri-O-actetyl-6-azido-6-deoxy-1-thio-β -d-galactopyranoside (4), methyl 2,3,4-tri-O-acetyl-6-azido-6-deoxy-α -d-mannopyranoside (7), and methyl 2,3,6-tri-O-acetyl-2-azido-2-deoxy-β -d-glucopyranoside (9), and tert-butyl-protected Fmoc-asparaginic acid propargylamide (10) gave the corresponding protected glycosyl amino acid building blocks 11, 13, 15, and 17 in 67% to 95% yield. The latter were converted into the corresponding pentafluorophenyl esters 12, 14, 16, and 18, which were used for a spot synthesis of a combinatorial library containing 256 glycotetrapeptides. The library was screened for lectin-binding affinity with the lectins Concanavalin A (Con A), phaseolus vulgaris (PHA-E), and galantus nivalis (GNA).     

Synthesis and Characterization of Novel Chiral (1R,2R)-1,2-Bis[5-(Aminomethylphospinic Acid)-1,3,4-Thiadiazol-2-YL]Ethane-1,2-Diols

Abstract

(1R,2R)-1,2-bis[5-(arylideneamino)-1,3,4-thiadiazol-2-yl]ethane-1,2-diol (2a–d) were synthesized by using appropriate aldehydes and (1R,2R)-1,2-bis(5-amino-1,3,4-thiadiazol-2-yl)ethane-1,2-diol (1) as a starting compound. Then, the phosphinic acid component (3a–d) were obtained from (2a–d) and hypophosporus acid. In addition, the structures of the novel chiral compounds (2a–d) and (3a–d) were confirmed by elemental analyses, IR, ¹H-NMR, ¹³C-NMR, and ³¹P-NMR spectra.

¹H NMR and ¹³C NMR spectra for 1, 2a, and 3a (Figures S1–S6) are available online in the Supplemental Materials.     

Acyl- und Alkylidenphosphane. XXIV. (N,N-Dimethylthiocarbamoyl)trimethylsilylphosphane und 1,2-Di(tert-butyl)-3-dimethylamino-1-thio-4-trimethylsilylsulfano-1λ5,2λ3-diphosphet-3-en

Acyl- and Alkylidenephosphines. XXIV. (N,N-Dimethylthiocarbamoyl)trimethylsilyl-phosphines and 1.2-Di(tert-butyl)-3-dimethylamino-1-thio-4-trimethylsilylsulfano-1λ⁵, 2λ³-diphosphet-3-ene In contrast to bis(trimethylsilyl)phosphines R? P[? Si(CH₃)₃]₂ 1 {R ? H₃C a ; (H₃C)₃C b ; H₅H₆ c ; H₁₁C₉ d ; (H₃C)₃Si e }, the more nucleophilic lithium trimethylsilylphosphides 4 react with N,N-dimethylthiocarbamoyl chloride already at ?78°C to give (N,N-dimethylthiocarbamoyl)trimethylsilylphosphines 2 . Working up the reaction, a dismutation of the mesityl derivative 2d is observed, whereas the tert-butyl compound 2b dissolved in toluene, eliminates dimethyl(trimethylsilyl)amine to form 1,2-di(tert-butyl)-3-dimethylamino-1-thio-4-trimethylsilyl-sulfano- 1λ⁵, 2λ³-diphosphet-3-ene 6b , nearly quantitatively within several days at +20°C.     

Synthesis of Anellated Pyranose Derivatives on the Basis of Levoglucosenone

ABSTRACT

1,6-Anhydro-2-(dicyanomethylene)-2,3-dideoxy-4-S-ethyl-4-thio-β-D-erythro-hexopyranose (1) reacted with tosyl azide or sulfur and triethylamine to furnish the 5-aza-10, 11-dioxatricyclo[6.2.1.0^2,6]undeca-2(6),3-diene-3-carbonitrile 2 and the 10,11-dioxa-5-thiatricyclo[6.2.1.0^2,6]undeca-2(6),3-diene-3-carbonitrile 3, respectively. The reactions of 1 with arylisothiocyanates furnished the 11,12-dioxa-5-thiatricyclo[7.2.1.0^2,7]dodeca-2(7),3-diene-3-carbonitriles 4 and 5. 3 underwent cyclization with triethyl orthoformate and ammonia or hydrazine hydrate to afford the 5,7-diaza-14,15-dioxa-9-thiatetracyclo[10.2.1.0^2,10.0^3.8]pentadecatetra(tri)enes 7 and 8, respectively.