Structures of new alkaloids sessilifoliamides A-D from Stemona sessilifolia

Four new Stemona alkaloids, sessilifoliamides A-D (1-4), were isolated from the roots of Stemona sessilifolia, along with five known alkaloids, stenine (5), 2-oxostenine (6), stemoninoamide (7), tuberostemonone (8), and neotuberostemonol (9). The structures and absolute configurations of the new alkaloids were determined by the spectral studies (HRMS, IR, ¹H, ¹³C, and 2D NMR), single-crystal X-ray analyses, and chemical correlations. The absolute configuration of 7 was also determined by the modified Mosher's method.     

Synthesis and structure of {{amino(triorganosilyl)carbene}pentacarbonyltungsten(0)} complexes and attempted synthesis of {[2-bis(trimethylsilyl)methyl-3-triorganosilyl-2H-azaphosphirene-κP]pentacarbonyltungsten(0)}

First examples of tungsten aminocarbene complexes [(OC₅)W{C(SiR¹_nR²_3-n)NH₂}] 2a-d (R¹ = Ph, R² = Me) were synthesized via ammonolysis of the corresponding methoxycarbene complexes 1a-d. They were characterized by NMR spectroscopy, MS, IR, UV/Vis and elemental analysis, and in the case of the C-triphenylsilyl derivative 2a by single-crystal X-ray structure analysis. The reaction of P-chloro alkylidenephosphane 3 with complexes 2a-d, meant to give 2H-azaphosphirene complexes, was monitored by ³¹P NMR spectroscopy to reveal the formation of the products 4-7, which were presumably formed via decomposition of the transient complexes 10a-d.     

Isolation,characterization, and NMR spectroscopic data of indole and oxindole alkaloids from Mitragyna speciosa

A new indole alkaloid, 7β-hydroxy-7H-mitraciliatine (1) and a new oxindole alkaloid, isospeciofoleine (2) together with nine known alkaloids were isolated from Mitragyna speciosa and characterized by NMR, CD, and MS spectroscopic data analyses. The ¹H and ¹³C NMR spectroscopic data of isospeciofoline (3), isorotundifoline (4), paynantheine (5), and 3-isopaynantheine (6) were also reported for the first time.     

A combinatorial access to 1,5-benzodiazepine derivatives and their evaluation for aldose reductase inhibition

Aryldiazepinothiophenones 4 were prepared from the reaction of o-phenylenediamines with acetone in the presence of 2-mercaptocarboxylic acids along with thiazolobenzodiazepines 6, thiazolobenzimidazoles 7 and 1,5-benzodiazepines 5, which were obtained as by-products. The benzodiazepinothiophenones 4a-d and the benzodiazepines 5a-d were also isolated from the reaction of o-phenylenediamines 1a-c with phorone. Structural assignments of the new compounds as well as complete assignment of ¹H and ¹³C NMR signals were based on the analysis of their ¹H and ¹³C NMR (1D and 2D), IR, MS and elemental analysis data. Compounds 4 were evaluated for aldose reductase inhibition and also as antioxidants.     

Synthesis and properties of 4,9-methanoundecafulvenes and their transformation to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones: photo-induced autorecycling oxidizing reaction toward amines

The synthesis and properties of 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-trione] derivatives 8a,b were studied. Their structural characteristics were investigated on the basis of the ¹H and ¹³C NMR and UV-vis spectra. The rotational barrier (ΔG^‡) around the exocyclic double bond of 8a was found to be 12.55 kcal mol⁻¹ by the variable temperature ¹H NMR measurement. The electrochemical properties of 8a,b were also studied by CV measurement. Furthermore, the transformation of 8a,b to 3-substituted 7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1H,3H)-diones 16a,b was accomplished by oxidative cyclization using DDQ and subsequent ring-opening and ring-closure. The structural details and chemical properties of 16a,b were clarified. Reaction of 16a with deuteride afforded C13-adduct 19 as the single product, and thus, the methano-bridge controls the nucleophilic attack to prefer endo-selectivity. The photo-induced oxidation reaction of 16a and a vinylogous compound, 3-methylcyclohepta[4,5]furo[2,3-d]pyrimidine-2,4(3H)-dione 2a, toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 6.1-64.0 (for 16a) and 2.7-17.2 (for 2a), respectively.     

Quinoxalines. Part 12: Synthesis and structural study of 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines—the dehydrogenative cyclization with hydroxylamine hydrochloride

Starting with 2-acetylquinoxaline a novel class of heterocyclic compounds, the 1-(thiazol-2-yl)-1H-pyrazolo[3,4-b]quinoxalines 4, were prepared by following two different synthetic procedures: 2-acetylquinoxaline reacted with thiosemicarbazide to the thiosemicarbazones 1a which was (i) cyclized with α-halogeno ketones to the thiazoles 3. These compounds were dehydrogenated in acidic medium to the title compounds 4. (ii) The thiosemicarbazone 1a could be also dehydrogenated using NH₂OH·HCl to the thioamide 5a and these, finally, were cyclized with α-halogeno ketones to the title compounds 4. Only thiazole 3a was isolated, the other thiazoles 3 were dehydrogenated in a one-pot procedure. From the thioamide 5a also both the compounds 9, by reacting with dibromodiacetyl, and 10, by treatment with dimethyl acetylenedicarboxylate, were obtained. The analysis of both the ¹H and ¹³C NMR spectra was not straightforward but could be attained finally by employing the whole arsenal of 1D and 2D NMR spectroscopy.     

p-Sulfonatocalix[7]arene: synthesis, protolysis, and binding ability

Water-soluble p-sulfonatocalix[7]arene 1 has been synthesized in good yield through standard procedures and its conformational preferences have been investigated by Monte Carlo conformational searches. The acid-base properties of 1 were investigated by means of potentiometric titration, obtaining pK_a values in agreement with those reported for other p-sulfonatocalix[n]arene homologs. The binding ability of 1 toward organic quaternary ammonium cations such as Diquat (2), Paraquat (3), and Chlormequat (4) was investigated by means of ¹H NMR titrations in D₂O at pD=7.3, DOSY NMR measurements, and 2D ROESY NMR spectroscopy. Spectrofluorimetry proved to be a useful method for the determination of trace amounts of 2 and 3 in aqueous solution by using Acridine Orange bound to 1 as a chemical indicator.     

Neutral penta-coordinated diorganotin(IV) complexes derived from ortho-aminophenol Schiff bases: Synthesis, characterization and molecular structures

The one pot reactions carried among ortho-aminophenol, R₂SnO (R = Me or Ph) and acetyl acetone, 2-hydroxyacetophenone and 2-hydroxy-3-methylacetophenone led to six new diorganotin(IV) compounds Me₂SnL1 (1), Ph₂SnL1 (2), Me₂SnL2 (3) Ph₂SnL2 (4), Me₂SnL3 (5) and Ph₂SnL3 (6) (H2L1 = 2-(3-hydroxy-1-methyl-but-2-enylideneamino)-phenol, H2L2 and H2L3 = 2-[1-(2-hydroxyaryl)alkylideneamino]-phenol) in good yields. Combination of IR, ¹H, ¹³C and ¹¹⁹Sn NMR and X-ray diffraction techniques along with elemental analyses evidenced the formation of penta-coordinated monomeric species. The crystal structures of ligand H2L1 and complexes 1, 3 and 4 were determined by single crystal X-ray diffraction study. In the solid state, the ligand H2L1 exists as keto-enamine tautomeric form. There are N-H…O intra-molecular hydrogen bonds between amine and carbonyl groups. Diorganotin(IV) complexes 1, 3 and 4 are monomers with TBP (trigonal bipyramidal) geometry surrounding the tin atom. The O, N, O- tridentate ligand places its two oxygen donating atoms in the axial positions, and the nitrogen atom occupies one equatorial position. The two R groups attached to tin occupy the other two equatorial positions. The solution structures were predicted by ¹¹⁹Sn NMR spectroscopy.     

Acyclic tertiary diamines and 1,4,7,10-tetraazacyclododecane with fluorine-containing β-diketones: Leading to low melting ionic adducts

N,N,N′,N′-Tetramethylmethanediamine (1a), N,N,N′,N′-tetramethylethanediamine (1b), N,N,N′,N′-tetramethyl-1,3-propanediamine (1c), and N,N,N′,N′-tetramethyl-1,6-hexanediamine (1d) were reacted at 25 °C with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (2a), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedione (2b), 2-thenoyltrifluoroacetone (2c), and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (2d) to form the ionic adducts 3-18. 1,4,7,10-Tetraazacyclododecane (1e) reacted at 25 °C with β-diketones (2a-d) and 1,1,1-trifluoro-2,4-pentanedione (2e) to give ionic solids 19-23 in good yields. Some of the products are liquid at 25 °C and are thermally stable over long liquid ranges as determined by thermal gravimetric analyses. Single-crystal X-ray structure determinations show that compounds 9 and 21 crystallize in the monoclinic space groups P2(1)/c and P2(1)/n, respectively. All the new compounds were characterized by ¹H, ¹⁹F and ¹³C NMR, electrospray MS and/or elemental analyses.     

Synthesis and characterization of new Rh complexes bearing CO, PPh3 and chelating P,O- or Se,Se-ligands: Application to hydroformylation of styrene

The complexes [Rh(CO)(PPh₃){Ph₂PNP(O)Ph₂-P,O}] (3), [Rh(CO)₂{Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (5), and [Rh(CO)(PPh₃){Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (6), were synthesised by stepwise reactions of CO and PPh₃ with [Rh(cod){Ph₂PNP(O)Ph₂-P,O}] (2) and [Rh(cod){Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (4), respectively. The complexes 3, 5 and 6 have been studied by IR, as well as ¹H and ³¹P NMR spectroscopy. The ν(CO) bands of complexes 3 and 6 appear at approximately 1960 cm⁻¹, indicating high electron density at the Rh^I centre. The structure of complexes 3 and 6 has been determined by X-ray crystallography, and the ³¹P NMR chemical shifts have been resolved via low temperature NMR experiments. Both complexes exhibit square planar geometry around the metal centre, with the five-membered ring of complex 3 being almost planar, and the six-membered ring of complex 6 adopting a slightly distorted boat conformation. The C-O bond of the carbonyl ligand is relatively weak in both complexes, due to strong π-back donation from the electron rich Rh^I centre. The catalytic activity of the complexes 2, 3 and 6 in the hydroformylation of styrene has been investigated. Complexes 2 and 3 showed satisfactory catalytic properties, whereas complex 6 had effectively no catalytic activity.     

Caldaphnidines A-F, six new Daphniphyllum alkaloids from Daphniphyllum calycinum

Six new Daphniphyllum alkaloids, namely caldaphnidines A-F (1-6), together with eight known ones, deoxycalyciphylline B, deoxyisocalyciphylline B, bukittiggine, calycicine A, methyl homosecodaphniphyllate, daphnilactone B, and daphnezomines L-M, were isolated from the leaves and the seeds of Daphniphyllum calycinum. The structure of 1 was determined by a single-crystal X-ray diffraction study, and the structures of 2-6 were established by spectral methods, especially two-dimensional NMR techniques (¹H-¹H COSY, HMQC, HMBC, and NOESY).     

Synthesis of functional Δ-1,3,5-oxazaphospholene and 2H-1,4,2-diazaphosphole complexes via catalytic ring expansion reactions of a 2H-azaphosphirene complex

Catalytically-induced ring expansion of 2H-azaphosphirene complex 1 using ferrocenium hexafluorophosphate and acetone (2), diethylketone (3), cyclohexanone (4), benzaldehyde (5) or para-hydroxy-benzaldehyde (6) furnished selectively the Δ³-1,3,5-oxazaphospholene complexes 7-11, whereas with ortho- and para-hydroxy- or ortho- and para-amino-substituted benzonitriles the 2H-1,4,2-diazaphosphole complexes 16-19 were obtained. Two further findings are noteworthy: (1) The significant decreased reaction time in the case of the sterically more demanding carbonyl derivatives 2-4 and (2) the formation of diastereomers in the case of 10 and 11 with a ratio of 8:1 and 9:1, respectively. All products were characterized by NMR, MS and elemental analysis and the configuration of complexes 7 and 10a were determined by X-ray single-crystal diffraction analysis.     

Vincamajorines A and B,monoterpenoid indole alkaloids with new carbon skeletons from Vinca major

Two new monoterpenoid indole alkaloids, vincamajorines A (1) and B (2), were isolated from Vinca major. Their structures were elucidated by means of 1D and 2D NMR, and HREIMS spectroscopic data. The relative and absolute configurations were deduced by comparing the experimental ¹³C NMR, ECD spectra, and OR data with those theoretically calculated. Vincamajorine A (1) represents a new C₂₀ carbon skeleton arranged compactly in seven rings, and vincamajorine B (2) is an alkaloid with an unprecedented 6/5/7/5/6 pentacyclic ring system. A possible biosynthetic pathway was also proposed for the formation of 1 and 2.     

Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

Synthesis and evaluation of 1-deoxy-8-epi-castanospermine, 1-deoxy-8-hydroxymethyl castanospermine, and (6S,7S,8R,8aR)-8-amino-octahydroindolizine-6,7-diol

A short, versatile, and enantioselective synthesis of 1-deoxy-8-epi-castanospermine (5), 1-deoxy-8-hydroxymethyl castanospermine (6), and (6S,7S,8R,8aR)-8-amino-octahydroindolizine-6,7-diol (7) is achieved from a common template 12. The key step utilized is PET provoked amine radical cyclization of 11 to 12 in excellent diastereoselectivity. The exocyclic double bond at C-8 of the template is functionalized to obtain 5-7 as exclusive diastereomers. 1-Deoxy-8-epi-castanospermine exhibited inhibition of α- and β-galactosidase and β-glucosidase. Compounds 6 and 7 were found to be weak inhibitors of β-glucosidase.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.     

Microwave-assisted and conventional synthesis and stereogenic properties of monospirocyclotriphosphazene derivatives

The reactions of hexachlorocyclotriphosphazene, N₃P₃Cl₆, with N/O donor type N-alkyl or (aryl)-o-hydroxybenzylamines HO(C₆H₄)CH₂NHR(Ar), [R(Ar) = C(CH₃)₃ (1), Ph (2)] produce monospirocyclic tetrachlorocyclotriphosphazenes (1a and 2a). The geminal substituted cyclotriphosphazenes (1b, 1d, 2b and 2d) are obtained from the reactions of 1 equiv. of 1a and 2a with 2 equiv. of pyrrolidine or morpholine in THF, while the fully substituted phosphazenes (1c, 1e, 2c and 2e) are formed from the reactions of 1a and 2a with the excess pyrrolidine or morpholine in toluene, between 24 and 48 h. The microwave-assisted reactions of 1a and 2a with excess pyrrolidine or morpholine in toluene afford the fully substituted products with higher yields than those which were obtained by conventional methods. The structural investigations of the compounds have been verified by elemental analyses, ESI-MS, FTIR, ¹H, ¹³C, ³¹P NMR and HETCOR techniques. The crystal structure of 2a is determined by X-ray crystallography and the phosphazene ring is in the flattened boat form. Compounds 1b, 1d, 2b and 2d in which the spiro aryloxy moiety provides the one centre of chirality exist as racemates and the chirality has been confirmed by ³¹P NMR spectroscopy on addition of a chiral solvating agent (CSA), (S)-(+)-2,2,2-trifluoro-1-(9′-anthryl)ethanol.     

Synthesis, characterization and in vitro DNA binding studies of tin(IV) complexes of tert-butyl 1-(2-hydroxy-1-phenylethylamino)-3-methyl-1-oxobutan-2-yl carbamate

Tin(IV) complexes 1(a and b) and 2(a and b) of valine derived peptide derivatives were synthesized and characterized on the basis of elemental analysis, IR, ¹H, ¹³C, ¹¹⁹Sn NMR, ESI-MS spectra and molar conductance measurements. The C-Sn-C angle was estimated from ^I3C and ¹H NMR data ¹J(¹¹⁹Sn, ^I3C) = 623 Hz; solution ²J(¹¹⁹Sn, ¹H) = 93.04 Hz to be 149.9°. In vitro binding studies of complexes 1 and 2 under physiological conditions at room temperature with CT-DNA were carried out employing UV-visible, fluorescence, circular dichroism and viscometric studies. The binding affinity of the complexes was quantified by calculating the K_b values and it follows the order 2a > 1a > 2b > 1b. To further examine the specific mode of binding, the interaction of complexes 2(a and b) were carried out with 5′GMP and 5′TMP by using absorption and NMR (¹H, ³¹P) spectroscopy. The supercoiled pBR322 plasmid DNA cleavage activity of the complexes was ascertained by gel electrophoresis assay. The complexes cleave supercoiled pBR322 plasmid DNA efficiently into its nicked form at micromolar concentrations.     

Synthesis of thiazino[6,5-b]indole derivatives, analogues of the phytoalexin cyclobrassinin. A new method for preparation of 3-aminomethylindole

An efficient non-reductive synthesis of 3-aminomethylindole (6) was developed from gramine (1) via 3-phthalimidomethylindole (2). The reactions of amine 6 with substituted methyl dithiobenzoates gave 3-(arylthiocarbonylaminomethyl)indoles. The Hugerschoff ring-closure reactions of the thiobenzamide intermediates (11a-f) with phenyltrimethylammonium tribromide and subsequent basic treatment furnished 2-arylthiazino[6,5-b]indole derivatives (14a-f). By use of the latter bromine source, the phytoalexin cyclobrassinin (8) was prepared in a considerably higher yield than described previously. The structures of the novel products were elucidated by IR, ¹H and ¹³C NMR spectroscopy, including 2D-HMQC, 2D-HMBC and DEPT measurements.     

Synthesis and characterization of organotin(IV) compounds with Schiff base of o-vanillin-2-thiophenoylhydrazone

Seven Schiff base adducts of organotin(IV), RSnLCl₂, which L is o-vanillin-2-thiophenoylhydrazone, and R is n-C₄H₉ (1), Me (2), Ph (3), and [R₂SnL], which L is o-vanillin-2-thiophenoylhydrazone, R is n-C₄H₉ (4), Me (5), Ph (6), PhCH₂ (7) have been synthesized. Those products were characterized by elemental analysis, IR, ¹H, ¹³C and ¹¹⁹Sn NMR spectra. The crystal and molecular structures of compounds 1, 4, and 6 have been determined by X-ray single crystal diffraction. In the crystal of compound 1 the tin atom is rendered six-coordinate in a distorted octahedral configuration by coordinating with the N atom of the Schiff base ligand, in compounds 4 and 6 the central tin atoms are five-coordinate in distorted trigonal-bipyramidal geometry and the comparison of the IR spectra reveal that disappearance of the bands assigned to carboxyl unambiguously conforms the ligand coordinate with the tin atom in enol form.