Studies on the constituents of Broussonetia species VIII. Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U, from Broussonetia kazinoki Sieb

Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) in low yield. Broussonetines R, S and T were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R)-1-hydroxy-3-[6-(4-hydroxybutyl)-cyclohexy-2-on-1(6)-enyllpropyl] pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,10S)-1,10,13-trihydroxytridecyl] pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,5S)-1,5, 13-trihydroxy-10-oxo-tridecyl] pyrrolidine (3). And broussonetines U and V were proposed to be (2S,3S,4S)-2-hydroxymethyl-3, 4-dihydroxy-5-(9-oxo-13-hydroxytridecyl)-5-pyrroline (4), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)-9-oxo-13-hydroxy-3-tridecenyl] pyrrolidine (5), respectively, by spectroscopic and chemical methods.     

Enzymatic resolution, desymmetrization, and dynamic kinetic asymmetric transformation of 1,3-cycloalkanediols

An efficient desymmetrization of cis-1,3-cyclohexanediol to (1S,3R)-3-(acetoxy)-1-cyclohexanol ((R,S)-2a) was performed via Candida antarctica lipase B (CALB)-catalyzed transesterification, in high yield (up to 93%) and excellent enantioselectivity (ee's up to >99.5%). (R,R)-Diacetate ((R,R)-3a) was obtained in a DYKAT process at room temperature from (1S,3R)-3-acetoxy-1-cyclohexanol ((R,S)-2a), in a high trans/cis ratio (91:9) and in excellent enantioselectivity of >99%. Metal- and enzyme-catalyzed dynamic transformation of cis/trans-1,3-cyclohexanediol using PS-C gave a high diastereoselectivity for cis-diacetate (cis/trans = 97:3). The (1R,3S)-3-acetoxy-1-cyclohexanol (ent-(R,S)-2a) was obtained from cis-diacetate by CALB-catalyzed hydrolysis in an excellent yield (97%) and selectivity (>99% ee). By deuterium labeling it was shown that intramolecular acyl migration does not occur in the transformation of cis-monoacetate to the cis-diacetate.     

Studies on the constituents of Broussonetia species. VII. Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, as inhibitors of glycosidase, from Broussonetia kazinoki SIEB

Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, were isolated from the branches of Broussonetia kazinoki SIEB, (Moraceae). Broussonetines M, O, P, and Q were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(10S)-10,13-dihydroxy-tri decyl]pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)9-oxo-13-hydroxy-3- tridecenyl]pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)10-oxo-13-hydroxy-3-++ +tridecenyl]pyrrolidine (3), and (2R,3S,4R,5R)-2-hydroxymethyl-3-hydroxy-4-(beta-D-glucopyranosyloxy++ +)-5-[10-oxo-13-(beta-D-glucopyranosyloxy)tridecyl]pyrrolidine (4) respectively, by spectroscopic and chemical methods. 1-4 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.     

A serendipitous synthesis of (+)-gregatin B, second structure revisions of the aspertetronins, gregatins, and graminin A, structure revision of the penicilliols

A (DHQN)(2)AQN-promoted asymmetric dihydroxylation (92% ee) of the allyl chloride derived from enynol (E)-13 and an 8-step sequence provided access to the hydroxyethylated furanone (R)-21. Oxidation with MnO(2) furnished 50% furanone (+)-(R)-2a and 2.7% isomeric furanone (+)-(R)-3a. (R)-2a possesses the accepted constitution of (+)-gregatin B but its spectra are different. Surprisingly, (+)-(R)-3a equals the natural product. Analogous structure reassignments are due for the gregatins A and C-E, the aspertetronins A-B, graminin A, and the penicilliols A and B.     

Asymmetric synthesis of (1R,2S,3R)-3-methylcispentacin and (1S,2S,3R)-3-methyltranspentacin by kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate

Conjugate addition of lithium dibenzylamide to tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate occurs with high levels of stereocontrol, with preferential addition of lithium dibenzylamide to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the 3-methyl substituent. High levels of enantiorecognition are observed between tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate and an excess of lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide (10 eq.) (E > 140) in their mutual kinetic resolution, while the kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds to give, at 51% conversion, tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate consistent with E > 130, and in 39% yield and 99 +/- 0.5% de after purification. Subsequent deprotection by hydrogenolysis and ester hydrolysis gives (1R,2S,3R)-3-methylcispentacin in > 98% de and 98 +/- 1% ee. Selective epimerisation of tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate by treatment with KO'Bu in 'BuOH gives tert-butyl (1S,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate in quantitative yield and in > 98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving (1S,2S,3R)-3-methyltranspentacin hydrochloride in > 98% de and 97 +/- 1% ee.     

Synthesis of trimethyl (2S,3R)- and (2R,3R)-[2-2H1]-homocitrates and dimethyl (2S,3R)- and (2R,3R)-[2-2H1]-homocitrate lactones-an assay for the stereochemical outcome of the reaction catalysed both by homocitrate synthase and by the Nif-V protein

Trimethyl (3R)-homocitrate 17, trimethyl (2S,3R)-[2-2H1]-homocitrate 17a and (2R,3R)-[2-2H1]-homocitrate 17b, as well as dimethyl (3R)-homocitrate lactone 18, (2S,3R)-[2-2H1]-homocitric lactone 18a and (2R,3R)-[2-2H1]-homocitric lactone 18b have been synthesised. D-quinic acid 12 was used as the source of the (3R)-centre in the unlabelled target compounds 17 and 18. (2)-Shikimic acid 19 and the (2)-[2-2H]-shikimic acid derivative 32 respectively were used in the synthesis of the labelled compounds. In the latter syntheses, Sharpless directed epoxidation of the olefin in the 5-deoxy ester diols 23 and 35 ensured a reaction from the same face as the allylic and homoallylic alcohols, and the reduction of the protected epoxides 25 and 37 ensured that the label was introduced in a stereoselective manner. The 1H NMR spectra of the labelled products present an assay for the stereochemistry of the biological reactions catalysed by homocitrate synthase and by the protein from the nifV gene.     

Aluminacyclopropene: syntheses, characterization, and reactivity toward terminal alkynes

Reactions of LAl with ethyne, mono- and disubstituted alkynes, and diyne to aluminacyclopropene LAl[eta2-C2(R1)(R2)] ((L = HC[(CMe)(NAr)]2, Ar = 2,6-iPr2C6H3); R1 = R2 = H, (1); R1 = H, R2 = Ph, (2); R1 = R2 = Me, (3); R1 = SiMe3, R2 = C[triple bond]CSiMe3, (4)) are reported. Compounds 1 and 2 were obtained in equimolar quantities of the starting materials at low temperature. The amount of C2H2 was controlled by removing an excess of C2H2 in the range from -78 to -50 degrees C. Compound 4 can be alternatively prepared by the substitution reaction of LAl[eta2-C2(SiMe3)2] with Me3SiC[triple bond]CC[triple bond]CSiMe3 or by the reductive coupling reaction of LAlI2 with potassium in the presence of Me3SiC[triple bond]CC[triple bond]CSiMe3. The reaction of LAl with excess C2H2 and PhC[triple bond]CH (<1:2) afforded the respective alkenylalkynylaluminum compounds LAl(CH=CH2)(C[triple bond]CH) (5) and LAl(CH=CHPh)(C[triple bond]CPh) (6). The reaction of LAl(eta2-C2Ph2) with C2H2 and PhC[triple bond]CH yielded LAl(CPh=CHPh)(C[triple bond]CH) (7) and LAl(CPh=CHPh)(C[triple bond]CPh) (8), respectively. Rationally, the formation of 5 (or 6) may proceed through the corresponding precursor 1 (or 2). The theoretical studies based on DFT calculations show that an interaction between the Al(I) center and the C[triple bond]C unit needs almost no activation energy. Within the AlC2 ring the computational Al-C bond order of ca. 1 suggests an Al-C sigma bond and therefore less pi electron delocalization over the AlC2 ring. The computed Al-eta2-C2 bond dissociation energies (155-82.6 kJ/mol) indicate a remarkable reactivity of aluminacyclopropene species. Finally, the 1H NMR spectroscopy monitored reaction of LAl(eta2-C2Ph2) and PhC[triple bond]CH in toluene-d8 may reveal an acetylenic hydrogen migration process.     

Chiron approach to the synthesis of (2S,3R)-3-hydroxypipecolic acid and (2R,3R)-3-hydroxy-2-hydroxymethylpiperidine from D-glucose

The first chiron approach from d-glucose for the total synthesis of (2 S,3 R)-3-hydroxypipecolic acid (-)-1a and (2R,3R)-3-hydroxy-2-hydroxymethylpiperidine (-)-2a is reported. The synthetic pathway involves conversion of d-glucose into 3-azidopentodialdose (5) followed by the Wittig olefination and reduction to give the piperidine ring skeleton (8) with a sugar appendage that on cleavage of an anomeric carbon followed by oxidation gives (-)-1a which on reduction affords (-)-2a.     

Tri-chlorido, 2-methylallyl and 2-butenyl tert-butylimido niobium and tantalum complexes: synthesis, multinuclear NMR spectroscopy and reactivity

Pseudooctahedral complexes [MCl(3)(NtBu)L(2)] (M = Nb, L = py 1, ? tmeda 3; M = Ta, L = py 2, ? tmeda 4) have been studied by spectroscopic methods. By a VT (1)H NMR experiment a mutual exchange process between the py(ax) and py(free) in the complexes 1-2 was observed, whereas (13)C and (15)N NMR studies showed in the complexes 3-4 a tmeda ligand with an axial/equatorial coordination mode. The reaction of 2 with 3 equiv of Grignard reagent produces the methathesis products [TaR(3)(NtBu)] (R = CH(2)CMeCH(2)5, CH(2)CHCHCH(3)6) in which 2-methylallyl and 2-butenyl groups appear with a η(3)- and σ-coordination mode, respectively. When, toluene solutions of the compounds 5-6 were treated with 2 equiv of 2,6-dimethylphenylisocyanide the imido bisiminoacyl compounds [TaR(NtBu){C(R)NAr-κ(1)C}(2)] (Ar = 2,6-Me(2)C(6)H(3); R = CH(2)CMeCH(2)7, CH(2)CHCHCH(3)8) can be isolated, via an imido iminoacyl intermediate [TaR(2)(NtBu){C(R)NAr-κ(1)C}] (Ar = 2,6-Me(2)C(6)H(3); R = CH(2)CMeCH(2)9) as we have observed in the treatment of 5 with 1 equiv of isocyanide; however, the analogous reaction between 5 and COPh(2) leads to the formation of the trisalkoxo imido compound [Ta(OCPh(2)R)(3)(NtBu)] (R = CH(2)CMeCH(2)10). All new complexes were studied by IR and multinuclear NMR spectroscopy.     

Synthesis, helicity, and chromism of optically active poly(phenylacetylene)s carrying different amino acid moieties and pendant terminal groups

Functional phenylacetylene derivatives containing l-alanine and l-leucine moieties with chiral menthyl and achiral n-octyl terminal groups {HC[triple bond]C-C6H4-p-CONHCH(R)CO2R': R = CH3, R'= (-)-(1R,2S,5R)-menthyl [1(-)]; R = CH2CH(CH2)3, R' = (-)-(1R,2S,5R)-menthyl [2(-)]; R'= CH2CH(CH2)3, R' = (+)-(1S,2R,5S)-menthyl [2(+)]; R'= CH2CH(CH2)3, R' = (CH2)7CH3 (2o)} are synthesized. Polymerizations of the acetylene monomers are effected by organorhodium catalysts, giving corresponding polymers P1(-), P2(-), P2(+), and P2o of high molecular weights (Mw up to 1.2 x 10(6)) in high yields (up to 89%). The polymers are thermally stable (Td >or= 300 degrees C) and soluble in common organic solvents. The polymer structures are characterized by IR, NMR, UV, and CD spectroscopies. Intense CD signals are observed in the visible spectral region, indicating that the polymer chains are taking a helical conformation with an excess of preferred handedness. The backbone conjugation and chain helicity of the polymers can be tuned by changing their molecular structures [(a)chiral pendant groups] and by applying external stimuli (solvent and pH). Addition of trifluoroacetic acid to the polymer solutions decreases their molar ellipticities and enhances their backbone conjugations, inducing a halochromism with a continuous and reversible color change (yellow <==> red).     

The synthesis, structure and ethene polymerisation catalysis of mono(salicylaldiminato) titanium and zirconium complexes

The silyl ethers 3-But-2-(OSiMe3)C6H3CH=NR (2a-e) have been prepared by deprotonation of the known iminophenols (1a-e) and treatment with SiClMe3 (a, R = C6H5; b, R = 2,6-Pri2C6H3; c, R = 2,4,6-Me3C6H2; d, R = 2-C6H5C6H4; e, R = C6F5). 2a-c react with TiCl4 in hydrocarbon solvents to give the binuclear complexes [Ti{3-But-2-(O)C6H3CH=N(R)}Cl(mu-Cl3)TiCl3] (3a-c). The pentafluorophenyl species 2e reacts with TiCl4 to give the known complex Ti{3-But-2-(O)C6H3CH=N(R)}2Cl2. The mononuclear five-coordinate complex, Ti{3-But-2-(O)C6H3CH=N(2,4,6-Me3C6H2)}Cl3 (4c), was isolated after repeated recrystallisation of 3c. Performing the dehalosilylation reaction in the presence of tetrahydrofuran yields the octahedral, mononuclear complexes Ti{3-But-2-(O)C6H3CH=N(R)}Cl3(THF) (5a-e). The reaction with ZrCl4(THF)2 proceeds similarly to give complexes Zr{3-But-2-(O)C6H3CH=N(R)}Cl3(THF) (6b-e). The crystal structures of 3b, 4c, 5a, 5c, 5e, 6b, 6d, 6e and the salicylaldehyde titanium complex Ti{3-But-2-(O)C6H3CH=O}Cl3(THF) (7) have been determined. Activation of complexes 5a-e and 6b-e with MAO in an ethene saturated toluene solution gives polyethylene with at best high activity depending on the imine substituent.     

Synthesis, characterization, and reaction of aluminum halide amides supported by a bulky beta-diketiminato ligand

Monomeric aluminum chloride amides with the general formula LAl(Cl)NR2 (1, R = Me; 2, R = iPr; 3, R = SiMe 3; L = HC[C(Me)N(Ar)]2; Ar = 2,6- iPr2C6H3) were prepared by selected routes. Treatment of LAlBr 2 (4) and LAlI2 with LiNMe2 yielded LAl(Br)NMe2 (5) and LAl(I)NMe2 (6), respectively. The alkylation of 1 and 2 with MeLi gave the corresponding methylated compounds LAl(Me)NR2 (7, R = Me; 8, R = iPr); however, no reaction of 3 with MeLi was observed because of steric hindrance. Subsequent fluorination of 1- 3 afforded LAl(F)NR2 (9, R = Me; 10, R = iPr; 11, R = SiMe3). Compounds 1-11 were characterized by multinuclear NMR, electron impact mass spectrometry, and IR. The constitution of compounds 1-3 was confirmed by single-crystal X-ray diffraction studies.     

Synthesis, characterization, and materials chemistry of Group 4 silylimides

This paper focuses on the development of potential single source precursors for M-N-Si (M = Ti, Zr or Hf) thin films. The titanium, zirconium, and hafnium silylimides (Me(2)N)(2)MNSiR(1)R(2)R(3) [R(1) = R(2) = R(3) = Ph, M = Ti(1), Zr (2), Hf (3); R(1) = R(2) = R(3) = Et, M = Ti (4), Zr (5), Hf (6); R(1) = R(2) = Me, R(3) = (t)Bu, M = Ti (7), Zr (8), Hf (9); R(1) = R(2) = R(3) = NMe(2), M = Ti (10), Zr (11), Hf (12)] have been synthesized by the reaction of M(NMe(2))(4) and R(3)R(2)R(1)SiNH(2). All compounds are notably sensitive to air and moisture. Compounds 1, 2, 4, and 7-10 have been structurally characterized, and all are dimeric, with the general formula [M(NMe(2))(2)(μ-NSiR(3))](2), in which the μ(2)-NSiR(3) groups bridges two four-coordinate metal centers. The hafnium compound 3 possesses the same basic dimeric structure but shows additional incorporation of liberated HNMe(2) bonded to one metal. Compounds 11 and 12 are also both dimeric but also incorporate additional μ(2)-NMe(2) groups, which bridge Si and either Zr or Hf metal centers in the solid state. The Zr and Hf metal centers are both five-coordinated in these species. Aerosol-assisted CVD (AA-CVD) using 4-7 and 9-12 as precursors generates amorphous films containing M, N, Si, C, and O; the films are dominated by MO(2) with smaller contributions from MN, MC and MSiON based on XPS binding energies.     

The monolanthanide-containing silicotungstates [Ln(beta2-SiW11O39)2]13- (Ln = La, Ce, Sm, Eu, Gd, Tb, Yb, Lu): a synthetic and structural investigation

We have synthesized and structurally characterized the monolanthanide-containing polyanions [Ln(beta2-SiW11O39)2]13- (Ln = La (1), Ce (2), Sm (3), Eu (4), Gd (5), Tb (6), Yb (7), Lu (8)). Synthesis was accomplished by reaction of the respective lanthanide ion with the monolacunary Keggin-type precursor [beta2-SiW11O39]8- in a 1:2 molar ratio in 1 M KCl medium at pH 5. Polyanions 1-8 were isolated as potassium salts and then characterized by IR, single-crystal X-ray diffraction, and elemental as well as thermogravimetric analysis. The structures of 1-8 are composed of an eight-coordinated Ln3+ center sandwiched by two chiral (beta2-SiW11O39) units. Large Ln3+ ions appear to favor an (R,R) (or (S,S)) configuration (point group C2) of the Keggin units, with an increasing amount of (R,S) (or (S,R)) configuration (point group C1) found in the solid state as the Ln3+ ion decreases in size. This trend is also supported by solution 183W NMR results for the diamagnetic La3+ and Lu3+ derivatives.     

Mononuclear gold(I) acetylide complexes with urea group: synthesis, characterization, photophysics, and anion sensing properties

A series of mononuclear gold(I) acetylide complexes with urea moiety, R'(3)PAuC≡CC(6)H(4)-4-NHC(O)NHC(6)H(4)-4-R (R' = cyclohexyl, R = NO(2) (2a), CF(3) (2b), Cl (2c), H (2d), CH(3) (2e), (t)Bu (2f), OCH(3) (2g); R' = phenyl, R = NO(2) (3a), OCH(3) (3b); R' = 4-methoxyphenyl, R = H (4a), OCH(3) (4b)), have been synthesized and characterized. The crystal structures of Ph(3)PAuC≡CC(6)H(4)-4-NHC(O)NHC(6)H(4)-4-NO(2) (3a) and (4-CH(3)OC(6)H(4))(3)PAuC≡CC(6)H(4)-4-NHC(O)NHC(6)H(5) (4a) have been determined by X-ray diffraction. Complexes 2a-2g, 3b, and 4a-4b show intense luminescence both in the solid state and in degassed THF solution at 298 K. Anion binding properties of complexes 2a-2g, 3a-3b, and 4a-4b have been studied by UV-vis and (1)H NMR titration experiments. In general, the log K values of 2a-2g with the same anion in THF depend on the substituent R on the acetylide ligand of 2a-2g: R = NO(2) (2a) > CF(3) (2b) ≥ Cl (2c) > H (2d) > CH(3) (2e) ≈ (t)Bu (2f) ≥ OCH(3) (2g). Complex 2a with NO(2) group shows the dramatic color change toward F(-) in DMSO, which provides an access of naked eye detection of F(-).     

New benzimidazole derivatives: Design,synthesis, docking,and biological evaluation

The aim of this study was to synthesize novel enaminonitrile derivatives starting from 2-aminobenzimidazole and utilize this derivative for the preparation of novel heterocyclic compounds and assess their function for biological activity screening. The key precursor N-(1H-benzo[d]imidazol-2-yl)carbonohydrazonoyl dicyanide (2) was prepared in pyridine by coupling of diazotized 2-aminobenzimidazole (1) with malononitrile. Compound 2 was subjected to react with various secondary amines such as piperidine, morpholine, piperazine, diphenylamine, N-methylglucamine, and diethanolamine in boiling ethanol to give the acrylonitriles (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(piperidin-1-yl)acrylonitrile (3), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-morpholinoacrylonitrile (4), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(piperazin-1-yl)acrylonitrile (5), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(diphenylamino)acrylonitrile (6), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)acrylonitrile (7), and (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(bis(2-hydroxyethyl)amino)acrylonitrile (8), respectively. It has been found that the behaviour of nitrile derivative 2 towards hydrazine hydrate to the creation of 4-((1H-benzo[d]imidazol-2-yl)diazenyl)-1H-pyrazole-3,5-diamine (9). The reaction of malononitrile with compound 2 in an ethanolic solution catalyzed with sodium ethoxide afforded 4-amino-1-(1H-benzo[d]imidazol-2-yl)-6-imino-1,6-dihydropyridazine-3,5-dicarbonitrile (11). Moreover, malononitrile reacted with 7 in a boiling ethanolic sodium ethoxide solution to give 2-(5-((1H-benzo[d]imidazol-2-yl)diazenyl)-4-amino-6-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)pyrimidin-2-yl)acetonitrile (14). Heating 7 in boiling acetic anhydride and pyridine afforded (2R,3R,4R,5S)-6-(((1E)-2-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-1-(N-acetylacetamido)-2-cyanovinyl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (15). When compound 15 is heated for a long time in refluxing DMF including a catalytic of TEA, cyclization occurs to give the corresponding (2R,3R,4R,5S)-6-((1-acetyl-3-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-4-amino-6-oxo-1,6-dihydropyridin-2-yl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (16). In addition, triethyl orthoformate was reacted with compound 7 in the presence of acetic anhydride to afford the corresponding ethoxymethyleneamino derivative (2R,3R,4R,5S)-6-(((1E)-2-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-2-cyano-1-(((E) ethoxymethylene)amino)vinyl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (17). Also, it has been found that heating a mixture of 7 with DMF/DMA in anhydrous xylene yielded compound (1E)-N'-((1E)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-2-cyano-1-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)vinyl)-N,N-dimethylformimidamide (18). In addition, compound 7, when reacted with several acid anhydrides, allowed the matching phthalimide derivatives 19–26. The results showed that compound 14 has significantly higher ABTS and antitumor activities than the other compounds. Molecular modelling was also studied for compounds 22 and 24. The viability of four many cell lines—the African green monkey kidney epithelial cells (VERO), human breast adenocarcinoma cell line (MCF-7), human lung fibroblast cell line (WI-38), and human hepatocellular liver carcinoma cell line (HepG2) was examined to determine the antitumor activities of the newly synthesized compounds. Also, it was found that compounds 9, 11, 15, 16, 22, 23, 24 and 25 are strong against HepG2 cell lines, while 16, 22, and 25 are strong against WI-38 cell lines. Moreover, it was also found that compounds 16 and 22 are strong against VERO cell lines. On the other hand, compounds 7, 14, 15, 16, and 22 are strong while the rest of the other compounds are moderate against the MCF-7 cell line. The result of docking showed that compound 24 got stabilized inside the pocket with a very promising binding score of ? 8.12 through hydrogen bonds with Arg184 and Lys179, respectively.     

Enols and thioenols of substituted cyanomonothiocarbonylmalonamides: structures, enolization vs. thioenolization, equilibria and conformations

Condensation of organic isothiocyanates with cyanoacetamides gave 24 N- and N'-substituted cyanomonothiocarbonylmalonamides in different tautomeric ratios i.e., amide-thioamides (TMA)R3NHCSCH(CN)CONR1R2 (12), thioamide-enols of amides (E) R3NHCSC(CN)=C(OH)NR1R2 (11)or amide-thioenols (TE) R3NHC(SH)=C(CN)CONR1R2 (13). The equilibrium constants (K(thioenol) =[TE]/[TMA] and K(enol) = [E]/[TMA]) in solution depend on R1, R2, R3 and the solvent. The %(E + TE)for NR1R2 increases in the order NMe2 < NHMe < NH2. The (K(thioenol) + K(enol)) in various solvents follows the order CCl4 > CDCl3 > C6D6 > THF-d8 > (CD3)2CO > CD3CN > DMF-d7 > DMSO-d6. The delta(OH) values are 16.46-17.43 and the delta(SH) values are 3.87-5.26 ppm in non polar solvents, e.g.,CDCl3 and 6.34-6.97 ppm in THF-d8 and CD3CN. An intramolecular O-H...O hydrogen bond leads to the preferred Z-configuration of the enols, and an N-H...O bond stabilizes the thioenols' preferred E-configuration with a non-bonded SH in solution. X-Ray crystallography revealed that systems with high %(E + TE) in solution mostly display the enols 11 in the solid state and systems with lower %(E +TE) in solution display structure 12. The differences in delta(OH), delta(NH), K(enol) and crystallographic data for analogous enol and thioenol systems are compared.     

Dinuclear manganese complexes containing chiral 1,4,7-triazacyclononane-derived ligands and their catalytic potential for the oxidation of olefins, alkanes, and alcohols

Five new 1,4,7-triazacyclononane-derived compounds, sodium 3-(4,7-dimethyl-1,4,7-triazacyclononan-1-yl)propionate (Na[LMe2R']) as well as the enantiopure derivatives (S)-1-(2-methylbutyl)-4,7-dimethyl-1,4,7-triazacyclononane (S-LMe2R'), SS-trans-2,5,8-trimethyl-2,5,8-triazabicyclo[7.4.01,9]tridecane (SS-LBMe3), (S)-1-(2-hydroxypropyl)-4,7-dimethyl-1,4,7-triazacyclononane (S-LMe2R), and (R)-1-(2-hydroxypropyl)-4,7-dimethyl-1,4,7-triazacyclononane (R-LMe2R), have been synthesized. Reaction of manganese dichloride with the chiral macrocycles S-LMe2R and R-LMe2R in aqueous ethanol gives, upon oxidation with hydrogen peroxide, the brown dinuclear Mn(III)-Mn(IV) complexes which are enantiomers, [Mn2(S-LMe2R)2(mu-O)2]3+ (S,S-1) and [Mn2(R-LMe2R)2(mu-O)2]3+ (R,R-1). The single-crystal X-ray structure analyses of [S,S-1][PF6]3.0.5(CH3)2CO and [R,R-1][PF6]3.0.5(CH3)2CO show both enantiomers to contain Mn(III) and Mn(IV) centers, each of which being coordinated to three nitrogen atoms of a triazacyclononane ligand and each of which being bridged by two oxo and by two chiral hydroxypropyl pendent arms of the macrocycle. The enantiomeric complexes S,S-1 and R,R-1 were found to catalyze the oxidation of olefins, alkanes, and alcohols with hydrogen peroxide. In the epoxidation of indene the enantiomeric excess values attain 13%. The bond selectivities of the oxidation of linear and branched alkanes suggest the crucial step in this process to be the attack of a sterically hindered high-valent manganese-oxo species on the C-H bond.     

Syntheses, reactions, and ethylene polymerization of half-sandwich titanium complexes containing salicylbenzoxazole and salicylbenzothiazole ligands

Half-sandwich titanium salicylbenzoxazole complexes CpTiLCl(2) 2a-2c [L = R-2-(benzo[d]xazol-2-yl)phenol (R = H (2a), R = 6-CH(3) (2b), R = 4-CH(3)-6-(t)Bu (2c)] and salicylbenzothiazole complexes CpTiLCl(2) 2d-2g [L = R-2-(benzo[d]thiazol-2-yl)phenol (R = H (2d), R = 6-CH(3) (2e), R = 6-(t)Bu (2f), R = 4-Cl (2g)] were synthesized by the reaction of CpTiCl(3) with the sodium salts of their corresponding precursors. Complexes 2a-2g were fully characterized by (1)H and (13)C NMR spectra and elemental analyses. The molecular structures of 2a and 2b were determined by single crystal X-ray diffraction methods. When activated by excess methylaluminoxane (MAO) these half-sandwich titanium complexes showed moderate to high activities for ethylene polymerization and produced high molecular weight polyethylenes. The half-sandwich titanium salicylbenzoxazole complexes (2a-2c) exhibited higher activities, of up to 1.23 × 10(6) g PE mol Ti(-1) h(-1) for the 2b/MAO system, than those of their analogues, half-sandwich titanium salicylbenzothiazole complexes (2d-2g).     

Effective, high-yielding, and stereospecific total synthesis of D-erythro-(2R,3S)-sphingosine from D-ribo-(2S,3S,4R)-phytosphingosine

The synthesis of naturally occurring D-erythro-(2R,3S,4E)-sphingosine from commercially available D-ribo-(2S,3S,4R)-phytosphingosine is described. The key step in the reaction sequence comprises TMSI/DBN promoted regio- and stereoselective oxirane opening of intermediate 2-phenyl-4-(S)-[(1S,2S)-1,2-epoxyhexadecyl]-1,3-oxazoline followed by the in situ trans-elimination of 2-phenyl-4-(S)-[(1S,2R)-1,2-dideoxy-2-iodo-1-trimethylsilyloxyhexadecyl]-1,3-oxazoline.