Synthesis Of Tri Research Articles

Synthesis of tri- and tetrasubstituted imidazoles

A reliable sequence that allows for regiospecific incorporation of four alkyl substituents on an imidazole ring has been developed. This procedure involves the addition of a substituted amino alcohol to a thioamide and subsequent oxidation with PDC. Unlike many imidazole syntheses, acid-sensitive functionality is tolerated given the mild conditions.

Novel Steroid Mimics: Synthesis of Tri‐ and Tetra‐Substituted Oxamides and Oxoamides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A Convenient Approach to Heterocyclic Building Blocks: Synthesis of Novel Ring Systems Containing a [5,6]Pyrano[2,3-c]pyrazol-4(1H)-one Moiety

Starting from commercially available educts, a straightforward synthetic route to new heterocyclic building blocks is exemplified with the one- or two-step synthesis of tri-, tetra-, or pentacyclic ring systems. Representatives of the following novel ring systems are prepared from 3-methyl-1-phenyl-2-pyrazolin-5-one and the corresponding o-halo-arenecarbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane: pyrimidino[4',5':5,6]pyrano[2,3-c]pyrazol-4(1H)-one, thieno[3',2':5,6]pyrano[2,3c]pyrazol- 4-(1H)-one, thieno[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H)-one, thieno[3'',2'':4',5']thieno[2',3':5,6]-pyrano[2,3-c]pyrazol-4(1H)-one, [1,3]dioxolo[5',6'][1]benzothieno[2',3':5,6]pyrano-[2,3-c]- pyrazol-4(1H)-one, pyridazino[4',3':5,6]pyrano[2,3-c]pyrazol-4(1H)-one and pyrazolo-[4'',3'':5',6']pyrido[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H)-one. While the latter two ring systems are directly obtained due to a spontaneous intramolecular substitution reaction, in the other reactions uncyclised 4-aroylpyrazol-5-ols are produced, which are cyclised into the target heterocycles in a subsequent synthetic step (i.e. treatment with NaH in DMF). Detailed NMR spectroscopic investigations ((1)H-, (13)C-, (15)N-) with the obtained compounds were undertaken to unambiguously prove the new structures.

Novel steroid mimics: synthesis of tri- and tetra-substituted oxamides and oxoamides

A series of dicarbonyl compounds have been designed and prepared to mimic the rigid tetracyclic core of estradiol and dihydrotestosterone. Non-symmetrical tri- and tetra-substituted oxamides were prepared by the sequential addition of primary and secondary amines to phenyl cholorooxoacetate. Oxoamides were prepared via a Friedel–Crafts acylation/amide coupling protocol. Crystallographic data shows a good correlation between the structure of the dicarbonyl mimic and dihydrotestosterone complexed with the androgen receptor suggesting the molecular scaffolds may well prove versatile platforms for ligand design.

Synthesis of highly-functionalised pyridines via hetero-Diels–Alder methodology: reaction of 3-siloxy-1-aza-1,3-butadienes with electron deficient acetylenes

Abstract The hetero-Diels–Alder reaction between 1-aza-3-siloxy-1,3-butadienes and electron deficient acetylenes is described. The reactivity of a range of α,β-unsaturated oximes and hydrazones is assessed in the synthesis of tri- and tetra-substituted pyridines bearing an oxygen functionality at C-3. Microwave irradiation has been employed to decrease the extended reaction times and increase the poor yields often associated with this reaction.

Intramolecular Double or Triple Suzuki Coupling Reaction of Substituted Di‐ or Tribromobenzenes. An Easy Synthesis of Fused Tri‐ or Tetracycles with a Benzene Core.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 3: Syntheses of tri- and tetra-aryl DPPs

Novel synthetic methodologies leading towards 2,3,5-triaryl- and 2,3,5,6-tetraaryl-2,5-dihydropyrrolo[3,4- c]pyrrole-1,4-diones (tri- and tetra-aryl-DPPs) and their derivatives have been investigated. Direct arylation of 3,6-diphenyl-DPP was possible using 1-fluoro-2,4-dinitrobenzene. Acylation of ethyl 2-aryl-4,5-dihydro-5-oxopyrrole-3-carboxylates with N-arylbenzimidoyl chlorides in the presence of a strong base gives the novel 2,3,6-triaryl-DPPs together with the corresponding uncyclised enamines. A new and simple method for the synthesis of ethyl 1,2-diaryl-4,5-dihydro-5-oxopyrrole-3-carboxylates has led to an alternative route to triaryl-DPPs via reaction with benzonitrile under basic conditions, and combination of this with the benzimidoyl chloride methodology has enabled the synthesis of variously substituted 2,3,5,6-tetraphenyl-DPPs.

Synthesis of tri- and tetracyclic diterpenes. Cyclisations promoted by SmI 2

Several tri- and tetracyclic diterpenes have been synthesised from zamoranic acid. The key step is the cyclisation of a dicarbonyl 13,14-secoderivative by SmI 2.

The Effects of P2O5 on the Synthesis of Tri-, Di-calcium Silicates, Tricalcium Aluminate and Ferrite Phase

ABSTRACT This study investigates the influence of P2O5 component on the formation reaction of clinker, which may be generated by using waste such as sewage sludge as raw material. To prepare tri-, di-calcium silicate, tricalcium aluminate, and ferrite phase, the mixture of raw materials was set at the modulus of LSF=91, SM=2.6 and IM=1.6. P2O5 component was added up to 2% with the increment of 0.5%. Mixed material was subjected to synthesis for 30 minutes at 1,450°C. The products generated were subjected to qualitative and quantitative analysis based on XRD measurement and SEM analysis. The result was that, as the content of P2O5 increased, the amount of tricalcium silicate tended to decrease, while that of dicalcium silicate and tricalcium aluminate increased. And the growth of their mineral phases also decreased with the increase of the content of P2O5.

Synthesis and X-ray crystal structures of organotri(2-furyl)phosphonium salts: effects of 2-furyl substituents at phosphorus on intramolecular nitrogen to phosphorus hypervalent coordinative interactions

The synthesis of tri(2-furyl)(8-quinolylmethyl)phosphonium bromide and 2-[2-tri(2-furyl)phosphoniophenyl]benzimidazole perchlorate is described, the latter involving a nickel(II)-catalysed displacement of bromine from 2-(2-bromophenyl)benzimidazole by tri(2-furyl)phosphine. X-ray structural studies of the phosphoniobenzimidazole salt reveals the existence of a significant hypervalent coordinative interaction between heterocyclic nitrogen and the phosphonium centre, which also appears to be retained in solution, the 31P NMR spectrum showing a significantly shielded phosphorus atom, δ 31P=ca. 40 ppm in CDCl 3. The structure of the phosphoniophenylbenzimidazole cation reveals major distortion of bond angles about phosphorus away from the idealised tetrahedral angles expected for a tetraarylphosphonium salt, in the range 102–116°. Three of the angles are reduced below the tetrahedral angle and three are increased, the structure about phosphorus approaching that of a trigonal bipyramid, in which the heterocyclic imino nitrogen forms part of a five-membered ring spanning apical–equatorial positions. The apical axis of the trigonal bipyramid is formed by this nitrogen atom and one of the 2-furyl groups, the apical axial bond angle (N2–P–C14) being an average of 178°. The remaining 2-furyl groups occupy equatorial positions, along with the phenyl ring. Significantly, the nitrogen–phosphorus distance is an average of 2.67 Å (for two independent molecules in the unit cell), being the shortest observed in structures of this type, a consequence of the electron-withdrawing properties of the 2-furyl substituents at phosphorus. The structure also shows edge to face associations of 2-furyl substituents of one cation with the phenyl ring of the benzimidazole unit of another cation. The perchlorate anion is hydrogen-bonded to the nitrogen bearing the hydrogen atom in the benzimidazole ring system. In contrast, the N–P interaction in the quinolylmethylphosphonium salt is much less developed, with an N–P distance of 3.511 Å, although there is considerable deformation of bond angles at phosphorus. The crystal structure is dominated by the existence of hydrogen-bonded interactions between the cation, anion and a molecule of water, and by face to face interactions between cations. Both salts undergo loss of a 2-furyl group on treatment with hydroxide ion.

Synthesis of tri- and tetramines containing two 2,3-dihydroxypyrrolidine moieties and their inhibitory activity toward α-mannosidases

Through the reductive amination of N-[(tert-butoxy) carbonyl]-2,5-dideoxy-2,5-imino-3,4-O-isopropylidene-L-ribose with tetramethylenediamine, hexamethylenediamine, 2,7-diaminofluorene, 4,4'-diaminodiphenylmethane and 1,4-(diaminomethyl) benzene, five tetramines containing two (2R, 3R, 4S)-2-aminomethylpyrrolidine- 3,4- diol moieties have been prepared and assayed for their inhibitory activities toward 24 glycosidases. Tetramines containing the tetramethylene or benzene-1,4-dimethylene linkers are more potent amannosidase inhibitors than simple (2R, 3R, 4S)-2-aminomethylpyrrolidine- 3,4-diols. Triamines such as (2S, 3R, 4S)-bis(3,4-dihydroxy-pyrrolidin-2-ethyl) amine were also prepared and shown to be better alpha-mannosidase inhibitors than (2S, 3R, 4S)- 2-(2-aminoethyl) pyrrolidin-3,4-diol.

Reaction of magnesium alkylidene carbenoids with lithium alpha-sulfonyl carbanions: a novel synthesis of tri- and tetra-substituted allenes from 1-chlorovinyl p-tolyl sulfoxides and sulfones.

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from ketones and chloromethyl p-tolyl sulfoxide, with ethylmagnesium chloride or isopropylmagnesium chloride at below -78 degrees C gave magnesium alkylidene carbenoids in about 90% yields. The reaction of the generated carbenoids with lithium alpha-sulfonyl carbanions was found to afford tri- and tetra-substituted allenes. Both cyclic ketones and acyclic ketones were useful in this procedure. However, the 1-chlorovinyl p-tolyl sulfoxides derived from aldehydes gave only rearranged products, acetylenes, under the reaction conditions. The magnesium alkylidene carbenoid derived from an optically active 1-chlorovinyl p-tolyl sulfoxide was treated with lithium alpha-carbanion of 1-naphthyl phenyl sulfone; however, the obtained allene was found to be racemic. The mechanism of this reaction is also discussed.

Design, synthesis and evaluation of peptide libraries as potential anti-HIV compounds, via inhibition of gp120/cell membrane interactions, using the gp120/cd4/fab17 crystal structure

The crystal structure of a gp120/CD4/Fab17b complex was analysed leading to the design of several peptide libraries in the hope of obtaining novel gp120/cell membrane receptor interaction inhibitors, especially inhibitors of gp120/CD4 and gp120/chemokine receptor interactions. Syntheses of tri- and tetra- and pentapeptides were performed via a solid phase synthesis methodology using a Rink Amide MBHA resin and a Fmoc strategy giving C-terminal amide form peptides. Compounds were assayed against C8166 cells infected by HIV-1 IIIB and screened using a gp120 binding assay and the FIGS reporter gene assay.

A convenient method for the preparation of highly substituted pyrimidines: Synthesis of tri‐ and tetra‐subsituted pyrimidines from 1,3‐dicarbonyl compounds and N,N,N‐tris‐(trimethylsilyl)amidines

AbstractA modification of the Pinner pyrimidine synthesis has been developed that utilizes trimethylsilyl amidines and results in greatly improved yield of highly substituted pyrimidines.

A chiral hexahydroindolizine as key intermediate in the synthesis of tri- and tetrahydroxyindolizidines

The highly stereoselective functionalization of hexahydro-3-oxo-indolizine 6 has been examined. The bishydroxylated product can be transformed successfully into the trihydroxyindolizidine 11 in 57% overall yield. In addition, a simple elimination process to give the α,β-unsaturated lactam 13 and a second highly stereoselective bishydroxylation can be used to synthesise the tetrahydroxyindolizidine 19 in 30% overall yield.

Syntheses of Tri- and Tetrahydroxylated 1-Amino-Heptanes

Syntheses of tri- and tetrahydroxylated 1-amino-heptanes from α-D-glucose are described.

Synthesis of novel benzene bridged polyalkynylazulenes

A synthesis of tri-, tetra- and pentaazulenylethynylbenzenes 3, 5 and 7 as well as 1,3,5-tripodal polyynes 11, 12, 14 and 15 by Pd/Cu-catalyzed cross-coupling reactions of the appropriate halides with the corresponding acetylenes are described.

Synthesis and conjugation of oligosaccharide fragments related to the immunologically reactive part of the circulating anodic antigen of the parasite Schistosoma mansoni

The immunoreactive part of the circulating anodic antigen (CAA) from the parasite Schistosoma mansoni is a threonine-linked polysaccharide consisting of →6)-[β-D-GlcpA-(1→3)]-β-D-GalpNAc-(1→ repeating disaccharides. In the framework of an immunochemical project, as a follow-up of earlier synthesized di- to tetrasaccharide CAA fragments, the synthesis of a spacer-containing pentasaccharide fragment, 3-(2-aminoethylthio)propyl (2-acetamido-2-deoxy-β-D-galactopyranosyl)-(1→6)-[(β-D-glucopyranosyluronic acid)-(1→3)]-(2-acetamido-2-deoxy-β-D-galactopyranosyl)-(1→6)-[(β-D-glucopyranosyluronic acid)-(1→3)]-2-acetamido-2-deoxy-β-D-galactopyranoside, is described. Moreover, 1-O-[3-(2-aminoethylthio)propyl]-N-acetyl-β-D-galactosamine was synthesized. Oxidation steps in the synthesis of tri- to pentasaccharide CAA fragments were performed using pyridinium dichromate and acetic anhydride. TEMPO-catalyzed oxidations were explored in the synthesis of 1-O-[6-aminohexyl]-β-D-glucuronic acid and 3-aminopropyl (2-acetamido-2-deoxy-β-D-galactopyranosyl)-(1→6)-[(β-D-glucopyranosyluronic acid)-(1→3)]-2-acetamido-2-deoxy-β-D-galactopyranoside, affording short reaction times and high yields. All synthesized compounds, including the earlier described 3-(2-aminoethylthio)propyl-spacered di-, tri-, and tetrasaccharide CAA fragments, were conjugated to BSA using squaric diester chemistry with coupling efficiencies in the range of 30–90%. The efficiency decreased when larger oligosaccharides were coupled to BSA. Finally, conformational analyses of the tri- and tetrasaccharide fragments were performed using Molecular Mechanics (MM) and Molecular Dynamics (MD) calculations.

A New Synthesis of Tri- and Tetrasubstituted Olefins Based on Thio- and Selenophosphates

Stereoselective synthesis of tri- and tetrasubstituted functionalized olefins and new phosphates bearing functionalized cyclic substituent has been developed using thiophosphates and selenophosphates as key intermediates.

Synthesis of tri- and tetrasaccharide fragments of the Shigella dysenteriae type 1 O-antigen deoxygenated and fluorinated at position 3 of the methyl α- d-galactopyranoside terminus

The blockwise synthesis of methyl alpha tri- and tetrasaccharide analogs of the biochemical repeating unit of the Shigella dysenteriae type 1 O-polysaccharide is described. Modifications include deoxygenation and deoxyfluorination at position 3 of the galactopyranoside residue. Methyl 4,6- O-benzylidene-3-deoxy- α- d- xylo-hexopyranoside ( 8) and methyl 4,6- O-benzylidene-3-deoxy-3-fluoro- α- d-galactopyranoside ( 9) were condensed with (2,3,4-tri- O-benzoyl- α- l-rhamnopyranosyl)-(1→3)-2,4-di- O-benzoyl- α- l-rhamnopyranosyl chloride to give, after deprotection, the target trisaccharide methyl α- l-rhamnopyranosyl-(1→3)- α- l-rhamnopyranosyl-(1→2)-3-deoxy- α- d- xylo-hexopyranoside and the corresponding fluorinated oligosaccharide. For the tetrasaccharide synthesis, the glycosyl acceptors 8 and 9 were condensed with the temporarily protected (2,4-di- O-benzoyl-3- O-chloroacetyl- α- l-rhamnopyranosyl)-(1→3)-2,4-di- O-benzoyl- α- l-rhamnopyranosyl chloride. Removal of the chloroacetyl group was followed by condensation of the resulting selectively deblocked trisaccharides with 3,4,6-tri- O-acetyl-2-azido-2-deoxy- α- d-glucopyranosyl chloride. Reduction and deprotection then gave the free methyl 2-acetamido-2-deoxy- α- d-glucopyranosyl-(1→3)- α- l-rhamnopyranosyl-(1→3)- α- l-rhamnopyranosyl-(1→2)-3-deoxy- α- d- xylo-hexopyranoside and the fluorinated analog.