Synthesis of 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil by selective elimination reactions

For the synthesis of y 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil (16), the precursor, 5′-O-benzoyl derivative (2),² was elaborated in a variety of ways. 1-(5′-O-Benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (4)² was benzoylated to N³-benzoyl-1-(2′,5′-di-O-benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (5), which directly yielded 2 on treatment with sodium benzoate. 1-(3′,5′-Di-O- benzoyl-2′-O-tosyl-β-D-lyxofuranosyl)uracil (8) and its 3′,5′-O-isopropylidene analog (10) resisted elimination reactions, thus proving absolute selectivity in the elimination of the derivatives of 1-β-D- lyxofuranosyl-uracil. Seeking a more economical path to 2, 1-(5′-O-benzoyl-β-D-lyxofuranosyl)uracil (11) was first benzoylated to give 2′,5′-di-O-benzoate (12), accompanied by 3′,5′-di- and 2′,3′,5′-tri-O- benzoate. Mesylation of the major product (12) gave 1-(2′,5′-di-O-benzoyl-3′-O-mesyl-β-D- lyxofuranosyl)uracil (15), which, on treatment with sodium benzoate, gave 2 in an highly improved yield. Basic hydrolysis on 2 gave compound 16.     

A regioselective 1,3-dipolar cycloaddition for the synthesis of novel spiro-chromene thiadiazole derivatives

A variety of 4′-(4-R-phenyl)-4-(methylthio)-2′-phenyl-2′H-spiro[chromene-2,5′-[1,2,3]thiadiazole] 5a–d and 5′-(4-R-phenyl)-4-(methylthio)-3′-phenyl-3′H-spiro[chromene-2,2′-[1,3,4]thiadiazole] 6a–d were synthesized regioselectively through the reaction of 4-(methylthio)-2H-chromene-2-thione 2 with diarylnitrilimines under refluxing dry chloroform. Whilst the reaction of 4-(allylthio)-2H-chromene-2-thione 3 with diarylnitrilimines under similar reaction conditions afforded the corresponding 4-(allylthio)-5′-(4-R-phenyl)-3′-phenyl-3′H-spiro[chromene-2,2′-[1,3,4]thiadiazole] 7a–d and 5-(4-R-phenyl)-2′-methyl-3-phenyl-2′,3′-dihydro-3H-spiro[[1,3,4]thiadiazole-2,4′-thieno[3,2-c]chromene] 9a–d as two unisolable diastereoisomeric forms. The structures of the obtained spiro cycloadduct thiadiazoles have been assigned by means of spectroscopic measurements.     

Reduced collagen cross links: the first synthesis of all the possible (2S,2′S)-stereoisomers of 5-hydroxylysinonorleucine and of 5,5′-dihydroxylysinonorleucine in enantiomerically pure form

The paper reports the first enantioselective synthesis of all the possible collagen reduced cross links as described: (2S,2′S,5R)- and (2S,2′S,5S)-5-hydroxylysinonorleucine 3a and 3b, (2S,2′S,5R,5′R)-5,5′-dihydroxylysinonorleucine 4a, (2S,2′S,5R,5′S)-5,5′-dihydroxylysinonorleucine 4b and (2S,2′S,5S,5′S)-5,5′-dihydroxylysinonorleucine 4c. The Williams’ glycine template methodology was used both for the introduction of a stereogenic at the α-position and for an easy protection of the amino acidic functionalities during the synthesis of the dimeric amino acids.     

A study of the claisen rearrangement of 7-cinnamyloxy benzo-γ-pyrones

The Claisen rearrangement of 7-O-cinnamyl noreugenin (2) yields 4′,5′ - dihydro - 5 - hydroxy - 2,4′ - dimethyl - 5′ - phenyl - furo (2′,3′: 7,8) chromone (6) as established by its NMR spectrum, whereas that of 7-cinnamyloxyflavone (10a) and 5 - hydroxy - 7 - cinnamyloxy - 2 - methylisoflavone (10b) afford the corresponding furo derivatives (12a and 12b respectively). All these rearrangements are symmetry-allowed but are accompanied by further reactions of thermal cyclisation via 3-membered cyclic intermediate (5) and/or dehydrogenation.     

A synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine via a bromine rearrangement during fluorination with MOST reagent

A facile method for the synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine 6 has been developed. Fluorination of 5′-O-acetyl-3′-β-bromo-3′-deoxyadenosine 3 with MOST gave 2′-β-bromo-3′-α-fluoro-2′,3′-dideoxyadenosine 4 via a rearrangement of the 3′-β-bromine to the 2′-β position during 3′-α fluorination. The 2′-β bromine was reduced by radical reduction and then the 5′-O-acetyl group was removed to afford 3′-α-fluoro-2′,3′-dideoxyadenosine 6 in good yield. A possible mechanism for the rearrangement is discussed.     

DFT study of the electronic and charge transfer properties of perfluoroarene–thiophene oligomers

The ground state structures of 5,5″-diperfluorophenyl-2,2′:5′,2″:5″,2‴-quaterthiophene (1), 5,5′-bis{1-[4-(thien-2-yl)perfluorophenyl]}-2,2′-dithiophene (2), 4,4′-bis[5-(2,2′-dithiophenyl)]-perfluorobiphenyl (3), 5,5″-diperfluorophenyl-2,2′:5′,2″-tertthiophene (4), 5,5′-diperfluorophenyl-2,2′-dihiophene (5), and 5,5-diperfluorophenylthiophene (6) have been optimized at the B3LYP/6-31G(d), B3LYP/6-31G(d,p), PBE0/6-31G(d), and PBE0/6-31G(d,p) level of theories. The B3LYP/6-31+G(d) and PBE0/6-31+G(d) level of theories have been applied to investigate the absorption spectra. The PBE0 functional is good to predict the C–S bond lengths while the C–F bond lengths are good envisaged with B3LYP functional. The increment of thiophene rings between two perfluoroarene rings leads to red shift in absorption spectra. The electron affinities are energetically destabilized while energetic stabilization of the radical-cation increases by decreasing the thiophene rings from four to one. The perfluoroarene rings leads to enhance the electron injection.     

Synthesis of 5-substituted-3-[(2′S,3′S)-3′-hydroxy-2′-hydroxymethyltetrahydrofuran-3′-yl]-1,2,4-oxadiazoles and their epimers

5-Phenyl-3-[(2′R,3′S)-3′-hydroxy-2′-dimethoxymethyltetrahydrofuran-3′-yl]-1,2,4-oxadiazole 10a and its epimer 11a, 5-methyl-3-[(2′R,3′S)-3′-hydroxy-2′-dimethoxymethyltetrahydrofuran-3′-yl]-1,2,4-oxadiazole 10b and its epimer 11b were synthesized from cyanohydrin benzoates 8a, 9a and cyanohydrin acetates 8b, 9b, respectively, by treatment with hydroxylamine in methanol via intramolecular transacylation and subsequent cyclization of the corresponding amidoximes. Hydrolysis and reduction of the dimethoxymethyl groups in the above compounds gave the desired compounds 12a, 13a, 12b and 13b.     

Two new natural substituted hexenophenones from the fungus Scytalidium

Two metabolites of the fungus Scytalidium Sp. FY strain, have been shown to be 5′-formyl-2′-hydroxy-4′-methoxy-(E)-4-hexenophenone 3 and 5′-formyl-2′-hydroxyl-4′-methoxy-(E,E)-sorbophenone 4.     

Synthesis of Schiff bases by aromatic amine condensation with 3,3′-bithiophenes-2,2′ and 4,4′-dicarbaldehydes

Reactions of aromatic amines with 3,3′-bithiophene-2,2′-dicarbaldehyde 1 and 3,3′-bithiophene-4,4′-dicarbaldehyde 2 gave the 2,2′-(N-(aryl)diimino)-3,3′-bithiophene 3 and 4,4′-(N-(aryl)diimino)-3,3′-bithiophene 4 in good yields. Orthophenylenediamine reacted with 1 and 2 to give dithieno[3,4-c;4′,3′-e]azepino[1,2-a]benzimidazole 5 and dithieno[2,3-c;3′,2′-e]azepino[1,2-a]benzimidazole 6. All these original products have been characterized by spectroscopic techniques and elemental analysis.     

Synthesis and pharmacological evaluation of 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine derivatives as platelet aggregation inhibitors

One pot synthesis and characterization of new 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridines (3a–k) using amides (2a–k) were reported. The prepared 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (3a) is a bioisostere of 4′-(6,7-dihydro-4H-thieno [3,2-c]pyridin-5-ylmethyl)-biphenyl-2-carboxylic acid (1), having good in vivo antithrombotic activity compared with Clopidogrel. The new tetrazole derivatives (3a–k) were screened for their in vitro activity as platelet aggregation inhibitors.     

Übergangsmetall-Carbin-Komplexe: CIII. Aktivierung von Ethylisocyanid an elektronenreichen Metallzentren; Synthese von einkernigen Wolfram-Aminocarbin-Komplexen des Typs Tp′(CO)2 WCN(R)Et (R  Me,Et)

A large-scale, high-yield synthesis of the aminocarbyne complexes Tp′(CO)₂WCN(R)Et (5: R  Me; 6: R  Et) [Tp′ = hydridotris(3,5-dimethylpyrazol-1-yl)borate] is reported, starting from Tp′W(CO)₃I (2). The first step of the synthetic procedure involves thermal decarbonylation of 2 with EtNC to give cis-Tp′W(CO)₂(CNEt)I (3). Complex 3 is then reduced with Na/Hg to give the metallate Na[Tp′W(CO)₂(CNEt)] (4). Finally, complex 4 is alkylated with RI (R  Me, Et) exclusively at the isocyanide nitrogen to give the aminocarbyne complexes 5 and 6. In contrast, the metallates Na[(η⁵-C₅R′₅)W(CO)₂(CNEt)] (R′  H, Me) undergo alkylation with RI at the metal centre to afford the W^II alkyl complexes cis/trans-(η-C₅R′₅)W(CO)₂(CNEt)R. This difference in reactivity is ascribed to the steric demands of the Tp′ ligand, which shields the metal centre from the incoming electrophile.     

Oxidative cleavage of the FeFe bond in [C5Me5Fe(CO)2]2 using ferrocinium ion: A facile route to the synthetically useful complexes [C5Me5Fe(CO)2(solvent)]+

Complexes of the type {Fp′(solvent)}⁺ PF₆^?, 3a–3d, (Fp′ = (η -C₅Me₅)Fe(CO)₂, solvent = THF, CH₃COCH₃, CH₃CN, or pyridine) are conveniently prepared by the reaction between Fp′₂ and Cp₂Fe⁺ PF₆ (Cp = η⁵-C₅H₅) in the solvent under ambient conditions. The complexes {Fp′L}⁺ PF₆^?, 3e–3g, (L = CO, PPh₃, P(OPh)₃) are readily prepared from {Fp′THF}⁺. Fp′H is formed by treatment of 3a with NaBH₄. Fp′SC(S)NMe₂ can be prepared from 3a or 3e and NaSC(S)NMe₂.     

Synthesis,structure, and conformation of terphenylene-derived azacalix[4]aromatics

Several novel azacalix[4]aromatics constituting terphenylene units have been synthesized via sequential nucleophilic aromatic substitution reactions of 5′-t-butyl-(1,1′:3′,1″-terphenyl)-3,3″-diamine 9 and 5′-t-butyl-(1,1′:3′,1″-terphenyl)– 4,4″-diamine 11 with 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride, respectively. The bridging –NH– functions of the tetra-nitro substituted azacalix[2]arene[2]terphenylenes 1 and 2 have been transformed to the corresponding –N(CH₃)– bridged azacalix[2]arene[2]terphenylenes 3 and 4 via N-alkylation. Single crystal X-ray analysis revealed that the terphenyl-3,3″-diamine derived azacalix[2]terphenylene[2]triazine 5 adopts a distorted chair conformation in the solid state, and the terphenyl-4,4″-diamine derived azacalix[2]terphenylene[2]triazine 6 was found to adopt a 1,3-alternate conformation.     

2′-Acetoxy-2-hydroxy-5-methoxybenzophenone: Photochemical synthesis,transacylation and cyclization to 2-methoxyxanthone

—_p-Methoxyphenyl salicylate2 gives 2,2′ - dihydroxy - 5 - methoxybenzophenone3 upon irradiation, but the yields are low both in hexane and in methanol.p-Methoxyphenylo-acetoxybenzoate1 undergoes photo-Fries rearrangement, affording 2′ - acetoxy - 2 - hydroxy - 5 - methoxybenzophenone4 in good yield. Compound4 is not stable in silica gel: it isomerizes to 2′ - acetoxy - 2 - hydroxy - 5′ - methoxybenzophenone5, that is also the major acetylation product of3 with acetyl chloride. Starting from1, 2-methoxyxanthorne7 is obtained in 57% overall yield.     

Effect of solvent on the regioselective synthesis of spiropyrazoles

1,3-Dipolarcycloaddition reactions of 6-arylmethylene-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones (1) with nitrilimines 3 were investigated in benzene and chloroform. The reaction products were 2′,4′,6,7,8,9-hexahydro-2′,4′,5′-triaryl spiro[benzocycloheptene-6(5H),3′(3H-pyrazol)-5-ones (4) or 2′,3′,6,7,8,9-hexahydro-2′,3′,5′-triaryl spiro[benzocycloheptene-6(5H),4′(4H-pyrazol)-5-ones (5). X-ray crystallographic analysis was carried out for compound 5b. It was found that the regioselectivity of the produced compounds was altered based on changing solvent type.     

Two new α,β-unsaturated butyrolactone derivatives from Pleione bulbocodioides

Two newα,β-unsaturated butyrolactone derivatives,4-(4″-hydroxybenzyl)-3-(3′-hydroxy-phenethyl)furan-2(5H)-one(1)and 3-(3′-hydroxyphenethyl)furan-2(5H)-one(2),together with one known phenolic compound(3),were isolated from the tubers of Pleione bulbocodioides(Franch.)Rolfe.Their structures were elucidated by analysis of spectroscopic data.     

New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands, (2R,3R)-[2-(2′-(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-[2-(diphenylphosphino)benzene][1,1′-binaphthalen-2,2′-diyl]phosphonite] ((S)-6). The analogous reaction of 4 with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2′-(diphenylphosphino)phenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers.     

Aminomethinylierung H-aktiver verbindungen in der reihe analgetischer wirkstoffe

Electrophilic attack of the active methylene group in 3-methyl-1-phenyl-5-pyrazolone (2) by s-triazine (1) leads to aminomethinylation of 2 with formation of 3-methyl-1-phenyl-4-aminomethylene-5-pyrazolone (4). Subsequent interaction of 4 with 2 explains the formation of 4,4′-methenyl-bis-[3-methyl-1-phenyl-5-pyrazolone (5). 1-Phenyl-3,5-pyrazolidinedione (6) reacts analogously with 1 forming 1-phenyl-4-aminomethylene-3,5-pyrazolidinedione (7). N,N′-Bis-indanyl-formamidine (9) results from the interaction of 2-amino-indane (8) with 1.     

Iodine catalyzed one-pot multi-component reaction to CF3-containing spiro[indene-2,3′-piperidine] derivatives

In the presence of a catalytic amount of molecular iodine (0.1 equiv.), the one-pot multi-component reaction of ethyl trifluoroacetoacetate 1, indan-1,3-dione 2, ammonium acetate 3 and aromatic aldehyde 4 mainly gave the ethyl-6′-hydroxy-1,3-dioxo-2′,4′-diaryl-6′-(trifluoromethyl)-1,3-dihydrospiro[indene-2,3′-piperidine]-5′-carboxylate derivatives 5, along with the minor product 2-trifluoromethyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine derivatives 6. A plausible reaction mechanism for the formation of 5, 6 was presented. The structures of compounds 5, 6 were fully confirmed by ¹H NMR, ¹⁹F NMR, MS, IR spectroscopies and elemental analysis or high resolution mass spectra (HRMS). Meanwhile, the representative 5a and 6h were further confirmed by XRD analysis.     

2,4-diaminothiazoles: Tautomeric structures and acetylation-substitution studies

NMR investigations on the hydrohalides of 2,4-diaminothiazole, 1, and on its 5-methyl and 5-phenyl derivatives, 2 and 3 respectively, show that they exist as a single nonaromatic tautomer with C-5 tetrahedral. This is also true for the free base 1, whereas 3 has C-5 trigonal. The di- and triacetyl derivatives of 1–3 are shown to be N,N′-di- and N,N,N′-triacetyl derivatives. Ethyl 2-cyano-3-ethoxyacrylate and 2-cyano-3-ethoxyacrylonitrile react with 1 at C-5.