Catechol oxidation: activity studies using electron-rich nitrogen-based ligands

We have studied the oxidation of catechol to o-quinone with atmospheric dioxygen at ambient conditions by in situ generated copper (II) complexes of five electron-rich nitrogen ligands: (3,5-dimethyl-pyrazol-1-yl)-methanol L1; 3-benzylamino-propionitrile L2; 3-[benzyl-(3,5-dimethyl-pyrazol-1-ylmethyl)-amino]-propionitrile L3; {3-[(2-cyano-ethyl)-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-amino]-propyl}-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-amino]-propionitrile L4 and 3-[{2-[(2-cyano-ethyl)-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-amino]-ethyl}-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)-amino]-propionitrile L5. We found that all complexes catalyze the oxidation reaction with different rates depending on three parameters: the nature of the ligand, the nature of ion salts, and the concentration of the complex. The combination of L3(CuSO₄) gave the highest rate of this activity about 8.71 μmol¹/L¹/min¹.     

Modification of 2-trifluoromethyl-1H-benzimidazole with hydroxyalkyl substituents

Alkylation of 2-(trifluoromethyl)-1H-benzimidazole with 4-bromobutyl acetate gave 4-[2-(trifluoromethyl)-1H-benzimidazol-1-yl]butyl acetate which was deacylated by the action of hydrogen chloride in anhydrous ethanol. 4-[2-(Trifluoromethyl)-1H-benzimidazol-1-yl]butan-1-ol thus formed showed a moderate tuberculostatic activity. Alkylation of the title compound with chloromethyloxirane afforded a mixture of 1-chloro-3-[2-(trifluoromethyl)-1H-benzimidazol-1-yl]-propan-2-ol and 1-(oxiran-2-ylmethyl)-2-trifluoromethyl-1H-benzimidazole. A new procedure was proposed for the synthesis of 2-[(2-trifluoromethyl-1Hbenzimidazol-1-yl)methoxy]ethyl acetate.     

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.     

Microbiological transformations—XII: Microbiological reduction of racemic 1-(2',2',3'-trimethyl-cyclopent-3'-en-1'-yl)propan-2-one and 1-(2',2',3'-trimethyl-cyclopent-3'-en-1'-yl)butan-2-one by rhodotorula mucilaginosa

The microbiological reduction of (±)-l-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-one (4) and (±)-1-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-butan-2-one (5) by Rhodotorula mucilaginosa was investigated. Both enantiomers of 4 are reduced stereospecifically to corresponding alcohols; (+)-(2S, l'R)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-ol (6) and (-)-(2S,l'S)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-ol (7). p ]The substrate selectivity in the reduction of 5 was observed: R enantiomer of 5 yields stereospecifically (+)-(2S,1'R)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-butan-2-ol (8) while S(-)5 remains unchanged.     

A Chemical Study of Burley Tobacco Flavour (Nicotiana tabacum L.) VII. Identification and synthesis of twelve irregular terpenoids,related to solanone,including 7,8-dioxabicyclo[3.2.1]octane and 4,9-dioxabicyclo[3.3.1]nonane derivatives

Twelve novel constituents isolated from Burley tobacco condensate by semi-preparative GLC. have been identified as (E)-3,4-epoxy-5-isopropyl-nonane-2,8-dione ( A ), exo-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)methyl ketone ( B ), exo-1-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)-ethanol ( C ), (E)-5-isopropyl-8-hydroxy-8-methyl-non-6-en-2-one ( D ), (E)-5-isopropyl-6,7-epoxy-8-hydroxy-8-methyl-nonan-2-one ( E ), endo-2-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)-propan-2-ol ( F ), 3,3,5-trimethyl-8-isopropyl-4,9-dioxabicyclo[3.3.1]nonan-2-ol ( G ), (E)-5-isopropyl-non-3-ene-2,8-diol ( H ), 5-isopropyl-nonane-2,8-diol ( I ), (E)-5-isopropyl-8-hydroxy-non-6-en-2-one ( J ), 5-isopropyl-8-hydroxy-nonan-2-one ( K ), and (E)-3-isopropyl-6-methyl-hepta-4,6-dien-1-ol ( L ). Compounds A–K were synthesized from norsolanadione ( 2 ), and compound L from 2-isopropyl-5-oxo-hexanal ( 15 ). The relative configuration of the bicyclic internal acetals B, C, F, G and their δ-keto-epoxide precursors A and E is discussed. All these Burley tobacco flavour components belong to a growing family of metabolites structurally related to solanone ( 1 ). They are believed to arise from the breakdown of cembrene-type precursors.     

(+)-Camphor-derived amino alcohols as ligands for the catalytic enantioselective addition of diethylzinc to benzaldehydes

1,7,7-Trimethyl-3-(pyrid-2-ylmethyl)bicyclo[2.2.1]heptan-2-ol 4 and its 2-phenyl, 2-methyl and 2-butyl analogs 5–7 were synthesized, characterized and used as ligands for the addition of diethylzinc to benzaldehydes. Best results were attained with 5 mol% of amino alcohol trans-4 (2-exo,3-endo), in hexane/toluene at rt. Thus, (1S)-1-phenylpropanol was obtained in 96% yield and 89% e.e. An increase of the size of the 2-substituent had a dramatic effect on enantioselectivity and yield.     

Chiral cyclopentadienyl ruthenium(II) complexes with P,P-ligands derived from (1R,2R)-1,2-diaminocyclohexane: Synthesis,crystal structures and catalytic activity in Diels–Alder reactions

Chiral cyclopentadienyl ruthenium(II) complexes [CpRu(L1–L3)Cl] (5–7) have been prepared by reaction of [CpRu(PPh₃)₂Cl] with chiral P,P-ligands (1R,2R)-1,2-bis(diphenylphosphinamino)cyclohexane (L1), N,N′-[bis-(3,3′-bis-tert-butyl-5,5′-bis-methoxy-1,1′-biphenyl-2,2′-diyl)phosphite]-(1R,2R)-1,2-diaminocyclohexane (L2) and N,N′-[bis-(R)-1,1′-binaphtyl-2,2′-diyl)phosphite]-(1R,2R)-1,2-diaminocyclohexane (L3). The molecular structures of 5 and 6 have been determined by single-crystal X-ray analysis. Studies on catalytic activity of the cations derived from (5–7) by treatment with AgSbF₆, are also reported.     

Synthesis of some tolperisone metabolites in racemic and optically active form

1-(4′-Carboxyphenyl)-2-methyl-3-(piperidine-1-yl)-propan-1-one M3, erythro-1-(4′-carboxyphenyl)-2-methyl-3-(piperidine-1-yl)-propan-1-ol M4 and threo-1-(4′-carboxyphenyl)-2-methyl-3-(piperidine-1-yl)-propan-1-ol M5, metabolites of the muscle relaxant tolperisone were synthesized in racemic and optically active forms.     

Reactions with 2-aminonicotinic acid,I Some 8-aza analogs of quinazolinones and derived tricyclic compounds

The fusion of 2-acetamidonicotinic acid witho-toluidine,p-bromoaniline oro-chloroaniline afforded the corresponding 3-aryl-2-methyl-pyrido-[2,3-d]pyrimidin-4(3H)-ones (4), the 8-aza analogs of 3-aryl-2-methyl-4-quinazolinones, alongside 2-aminonicotinic acid. 2-Methyl-3-2(2-methylphenyl)-pyrido[2,3-d]pyrimidin-4(3H)-one (4a), the 8-aza analog of methaqualone, was converted to the 2-substituted styryl derivatives6 by condensation with some aromatic aldehydes and to the tricyclic system, 10-aza-5,6-dihydro-3-hydroxy-5-(2-methylphenyl)-2-substituted-1H-pyrido [1,2-a] quinazoline-1,6-diones (8) by reaction with monosubstituted bis-2,4,6-trichlorophenyl malonates.     

Efficient stereoselective synthesis of a 1-hydroxymethyl-2-methylglycidol derivative

A highly stereoselective synthesis of (2R,3S)-3,4-epoxy-3-methyl-1-(triphenylmethyl)oxybutan-2-ol 3, which is a substructure found in some naturally-occurring bioactive compounds, was achieved starting from commercially available 3-methyl-2-buten-1-ol 4 in three steps, using two applications of the Sharpless asymmetric epoxidation as the key stereochemistry establishing reactions.     

Synthesis and structure of novel copper(II) complexes with pyrazole derived ligands and metal–ligand interaction in solution

Two new ligands of the coumarin type have been synthesized and characterized by ¹H, ¹³C NMR, IR and MS. The crystal and molecular structures of ligand 2, determined by the X-ray diffraction method, are presented. With copper(II) these ligands create solid complexes of the type CuLCl₂, where L is 5-(2-hydroxybenzoyl)-3-methyl-1-(2-pyridinyl)pyrazol-4-carboxylic acid methyl ester (2) or 3-methyl-1-(2-pyridinyl)-1H-chromene[4,3-c]pyrazol-4-on (3). The new copper(II) complexes have been characterized by elemental analysis and solid state FT-IR. The protonation constants of ligands 2 and 3 have been determined in 5% v/v 1,4-dioxane–water solution (25 °C). The coordination modes in the complexes with copper(II) are discussed for 2 on the basis of potentiometric and UV–Vis data.     

A transannular reaction during lithium ammonia reduction of an α,β-unsaturated ketone

The lithium-ammonia reduction of the α,β-unsaturated bicyclic dione 2-methyl-Δ^1,6-bicyclo[6,4,0]cyclododecene-5,9-dione 1 has been found to give two isomeric products 2α-methyl-5-oxo-6β-tricyclo[6,4,0,0^1,9] dodecan-9α-ol 2 and 2-β-methyl-5-oxo-6β-tricyclo[6,4,0,0^1,9]dodecan-9α-ol 3 involving a transannular reaction. Chemical and spectral evidence are presented to support the assigned structures. The stereochemistry of 2 arid 3 is also discussed.     

Asymmetric synthesis of N,O-diprotected (2S,3S)-N-methyl-δ-hydroxyisoleucine,noncoded amino acid of halipeptin A

The first enantioselective synthesis of N,O-diprotected (2S,3S)-N-methyl-δ-hydroxyisoleucine 4, starting from readily available (tert-butyldimethylsilyl)-2-butyn-1-ol 5, is described. The key steps of this stereochemical flexible synthetic route involve a silyl-assisted [3,3]-sigmatropic rearrangement, for the establishment of the correct stereoisomeric pattern, and a triethylsilane–TFA induced reduction of an oxazolidinone intermediate, to yield the requested N-methylation.     

Improved syntheses of precursors for PET radioligands [F]XTRA and [F]AZAN

Improved syntheses of 7-methyl-2-exo-[3′-(2-bromopyridin-3-yl)-5′-pyridinyl]-7-azabicyclo[2.2.1]heptanes (3) and 7-methyl-2-exo-[3’-(6-bromopyridin-2-yl)-5′-pyridinyl]-7-azabicyclo[2.2.1]heptanes (4), precursors for PET radioligands [¹⁸F]XTRA (1) and [¹⁸F]AZAN (2), involving a key Stille coupling step followed by deprotection of Boc group and N-methylation are described. The new synthetic procedures provided the title compounds in more than 40% overall yields.     

3-(4,5-Dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-ylmethyl)oxazolidines and 3-(4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-ylmethyl)perhydro-1,3-oxazines

3-(4,5-Dihydro-1H-pyrazol-1-ylmethyl)oxazolidines and 3-(4,5-dihydro-1H-pyrazol-1-ylmethyl)perhydro-1,3-oxazines were synthesized in 54–85% yield by reactions of α-amino alcohols and 3-aminopropan-1-ol, respectively, with formaldehyde and 4,5-dihydro-1H-pyrazoles.     

Synthesis of the antiepileptic (R)-Stiripentol by a combination of lipase catalyzed resolution and alkene metathesis

The enantiopure (ee >99%) antiepileptic (R)-(+)-Stiripentol has been stereoselectively synthesized via cross metathesis of 5-vinylbenzo[d][1,3]dioxole 1 and (R)-(+)-4,4-dimethylpent-1-en-3-ol (R)-(+)-2. A novel one-pot two-step pathway for the synthesis of 5-vinylbenzo[d][1,3]dioxole 1 starting from 3,4-dihydroxycinnamic acid has been introduced. A lipase catalyzed kinetic resolution access to enantiopure (R)-(+)-4,4-dimethylpent-1-en-3-ol (R)-(+)-2 (ee >99%) has also been developed.     

Phyto – Monoterpene linalool as precursor to synthesis epoxides and hydroperoxides as anti carcinogenic agents via thermal and photo chemical oxidation reactions

Linalool (I) was extracted from Zingiber officinale. The oxidation of linalool using m-chloroperbenzoic acid at room temperature gave the mixture of 2,2,6-trimethyl-6-vinyl-tetrahydro-pyran-3-ol (IIa) & 2-(5-methyl-5-vinyl- tetrahydro-furan-2-yl)-propan-2-ol (IIa′), which cannot be separated. Whereas, the photo-epoxidation of it using hydrogen peroxide gave the above mixture IIa/IIa′, beside 2,2,8-trimethyl-6-oxianyl-tetrahydro-pyran-3-ol (IIb). It was evaluated for anti-oxidant, using erythrocyte hemolysis and ABTS methods. It showed inhibitory effect in case of erythrocyte hemolysis and low inhibitory effect in case of ABTS method. Photosensitization reactions of linalool with tetraphenyl porphyrin or chlorophyll produced a mixture of two isomeric hydroperoxides, 7-hydroperoxy-3,7-dimethylocta-1,5-dien-3-ol (IIIa) & 6-hydroperoxy-3,7-dimethyl octa-1,7-dien-3-ol (IIIb), which can be successfully separated. On the other hand, the cytotoxic activity of linalool (I) was tested against epdermoid carcinoma (HEP2), it has medium effect. Whereas, in case of human prostate cancer (PC-3), it has weak effect. From this study concludes that ginger has good antioxidant potential and this spice can be used to produce novel natural antioxidants and flavoring agent like linalool which recommends it as an active therapy for humans. Monoterpene linalool abstract singlet oxygen (¹O₂) by photosensitization reactions to produce these hydroperoxides, which are caused relatively little oxidative DNA damage.     

Strukturelle Abwandlungen an Nukleotiden,Nukleosiden und Nukleosidbasen mit β-Acylvinylphosphoniumsalzen

β-Acetylvinyl-triphenylphosphonium bromide1 reacts with CMP to form the 3,N⁴-etheno-derivative {[6-(5′-phosphoribofuranosyl)-2-methyl-5-oxo-imidazo [1.2-c]pyrimidin-3-yl]-methyl}triphenyl-phosphonium bromide (2). Guanine affords mainly the lin. condensation product [(6-methyl-9-oxo-imidazo[1.2-a]-purin-7-yl)-methyl]triphenylphosphonium bromide (3) and the angular tricyclic product [(6-methyl-9-oxo-imidazo[2.1-b]purin-5-yl)-methyl]-triphenylphosphonium bromide (4). For comparison we synthesized the angular condensed heterocycle5, (6.8-dimethyl-9-oxo-imidazo[2.1-b]purin-5-yl)-methyl]triphenylphosphonium bromide, by reaction of 1-methylguanine with1, and the corresponding linear derivative6 [(4.6-dimethyl-9-oxo-imidazo[1.2-a]purin-7-yl)-methyl]-triphenylphosphoniumbromide from 3-methylguanine and1. AHofmann-type degradation of3 with the anion of diethyl malonate led to7, diethyl (6-methyl-9-oxo-imidazo[1.2-a]purin-7-yl)-methylmalonate, a compound whose structure resembles some Y-bases in t-RNA.Wittig reaction of the silylated nucleoside derivative8 a {[2-methyl-5-oxo-6-(2′.3′.5′-tris-trimethylsilyl)-ribofuranosyl-imidazo[1.2-c]pyrimidin-3-yl]methyl}-triphenylphosphonium bromide, with C₆H₅CHO resulted in the 2-methyl-3(ω-styryl)-6[2′.3′.5′-tris-(trimethylsilyl)]ribofuranosyl-imidazo[1.2-c] pyrimidin-5-one (9).     

Design and synthesis of self-included pillar[5]arene-based bis-[1]rotaxanes

Two strategies for the design of new pillar[5]arene-based mechanically self-interlocked molecules (MSMs) are reported here. The first strategy is based on the construction of an intermediate pseudo[1]rotaxane followed by the desired bis-[1]rotaxane. The other one is based on the construction of the desired bis-[1]-rotaxane directly via a condensation reaction through host-guest interactions between a mono-functionalized pillar[5]arene and the axle. This compound has interesting self-assembly properties in methanol and some extended applications of this compound will be reported in the near future.     

Oligothiophene-2-yl-vinyl bridged mono- and binuclear ruthenium(II) tris-bipyridine complexes: Synthesis, photophysics, electrochemistry and electrogenerated chemiluminescence

A series of mono- and binuclear ruthenium(II) tris-bipyridine complexes tethered to oligothienylenevinylenes have been synthesized and characterized by ¹H NMR, ¹³C NMR and TOF-MS spectrometry. Photophysics, electrochemistry and electrogenerated chemiluminescence (ECL) properties of these complexes are investigated. The electronic absorption spectra of the mononuclear ruthenium complexes show a significant red shift both at MLCT (metal-to-ligand charge transfer) and π-π^∗ transitions of oligothienylenevinylenes with increase in the number of thiophenyl-2-yl-vinyl unit. For the binuclear complexes these two absorption bands are overlapped. All the metal complexes have very weak emission compared to that of the reference complex Ru(bpy)²⁺₃. The first reduction potentials of all mononuclear ruthenium complexes are less negative than that of Ru(bpy)²⁺₃, due to the moderate electron-withdrawing effect of oligothienylenevinylenes. For binuclear ruthenium complexes, only one Ru(II/III) oxidation peak (E_1/2 = 0.96 V vs. Ag/Ag⁺) was observed, suggesting a weak interaction between two metal centers. Three successive reduction processes of bipyridine ligands are similar among all ruthenium complexes except for RuTRu, which has a very sharp peak owing to the accumulation of neutral product on the electrode surface. All these ruthenium complexes exhibited different ECL property in CH₃CN solution without any additional reductant or oxidant. For three mononuclear ruthenium complexes, the ECL intensity strengthens with increase in the number of thiophene-2-yl-vinyl unit. However, the ECL efficiency dramatically decreased in the binuclear ruthenium complexes. The ECL efficiencies of all the reported complexes do not exceed that of Ru(bpy)²⁺₃, where the ECL efficiency decreases in the order of RuTRu > Ru3T > Ru2T > RuT > Ru2TRu (RuT,bis-2,2′-bipyridyl-(4-methyl-4′-(2-thienylethenyl)-2,2′-bipyridine) ruthenium dihexafluorophosphate; Ru2T, bis-2,2′-bipyridyl-(4-methyl-4′-{(E)-2-[5-((E)-2-thienylethenyl)-thienylethenyl]}-2,2′-bipyridine) ruthenium dihexafluorophosphate; Ru3T, bis-2,2′-bipyridyl-(4-methyl-4′-{(E)-2-{(E)-2-[5-((E)-2-thienylethenyl)-thienylethenyl]}}-2,2′-bipyridine) ruthenium dihexafluorophosphate; RuTRu, bis-2,2′-bipyridyl-ruthenium-bis-[2-((E)-4′-methyl-2, 2′-bipyridinyl-4)-ethenyl]-thienyl-bis-2,2′-bipyridyl-ruthenium tetrahexafluorophosphate; Ru2TRu, bis-2,2′-bipyridyl-ruthenium-(E)-1,2-bis-{2-[2-((E)-4′-methyl-2,2′-bipyridinyl-4)-ethenyl]-thienyl}-ethenyl-bis-2,2′-bipyridyl-ruthenium tetrahexafluorophosphate).