Tri- and tetraphenylantimony propiolates: Syntheses and structures

The reaction of triphenylantimony with propiolic acid in the presence of hydrogen peroxide (molar ratios 1 : 2 : 1 and 1 : 1 : 1) in diethyl ether affords triphenylantimony dipropiolate Ph₃Sb[OC(O)C≡CH]₂ (I) and μ₂-oxobis[(propiolato)triphenylantimony] [Ph₃SbOC(O)C≡CH]₂O (II). Tetraphenylantimony propiolate Ph₄SbOC(O)C≡CH (III) is synthesized from pentaphenylantimony and propiolic or acetylenedicarboxylic acid in toluene. According to the X-ray diffraction data, the crystals of compounds I and III include two types of crystallographically independent molecules (a and b). The antimony atoms in molecules Ia, Ib, II, IIIa, and IIIb have the trigonal-bipyramidal coordination mode with different degrees of distortion. The OSbO and OSbC axial angles are 176.8(2)° (Ia, Ib), 170.17(15)°, 178.78(14)° (II), and 173.2(5)°, 174.4(5)° (IIIa, IIIb). The CSbC equatorial angles lie in the ranges 108.2(3)°–143.1(3)° (I), 109.0(2)°–131.0(2)° (II), and 113.1(4)°–125.4(4)° (III). The SbOSb angle in II is 141.55(19)°. The Sb-C bond lengths are 2.103(8)–2.141(5) (I), 2.105(5)–2.119(5) (II), and 2.076(12)–2.166(13) Å (III). The Sb-O distances increase in a series of I, II, and III: 2.139(6)–2.156(7) (Ia, Ib); 2.206(4), 2.218(3) (II); and 2.338(10), 2.340(10) Å (III).     

Synthesis and antiproliferative activity in vitro of new 2-aminobenzimidazole derivatives. Reaction of 2-arylideneaminobenzimidazole with selected nitriles containing active methylene group

A series of pyrimido[1,2-a]benzimidazole and α-cyanocinnamic acid derivatives have been synthesized in the reactions of Schiff bases 2–7 with selected nitriles containing an active methylene group: malononitrile 8–12, cyanoacetamide 13–16, benzyl cyanide 17–21, benzoylacetonitrile 22–24, cyanoacetate methyl ester 25–28 and benzylacetamide 29. The structures 8–29 were confirmed by the results of elementary analysis and their IR, ¹H-, ¹³C-NMR and MS spectra. The products 8–29 of various chemical structure pyrimido[1,2-a] benzimidazole 8–12, 14–16, 17–21, 23–24, 26 and α-cyanocinnamic acid derivatives 13, 22, 25, 27, 28 were obtained, which are of interest for biological studies or which can be substrates for further synthesis. The selected compounds 10, 13, 14, 17, 19, 21, 23–25 and 28 were screened for their antiproliferative activity in vitro against neoplastic and normal cell lines. The most active two compounds were: 2-(o-bromophenylene)-3-cyano-4-phenyl-1,2-dihydropyrimido[1,2-a]benzimidazole (24) and 3-cyano-4-phenyl-2-(2,4-dimethoxyphenyl)-1,2-dihydropyrimido[1,2-a]benzimidazole (23). However, similarly like cisplatin used as the control, they showed no selectivity towards cancer cells, by inhibiting proliferation of normal mouse fibroblasts in similar manner.      

Bis(tetraphenylantimony) succinate,malate, and tartrate: Syntheses and structures

The reactions of pentaphenylantimony with succinic, malic, and tartaric acids (mole ratio 2: 1) in toluene afford bis(tetraphenylantimony) succinate (I), malate (II), and tartrate (III) in yields of 98, 92, and 94%, respectively. According to the X_ray diffraction analysis results, molecules I and II are centrosymmetric. In compound II, the hydroxy group in the acid residue is disordered over two positions. Crystal III includes two types of crystallographically independent molecules (a and b). The antimony atoms in compounds I, II, IIIa, and IIIb have distorted trigonal bipyramidal coordination modes. The axial angles C_axSbO_ax are 166.80(8)° (I); 174.8(2)° (II); 176.4(4)°, 177.4(3)° (IIIa); and 173.3(4)°, 172.7(4)° (IIIb). The equatorial angles C_eqSbC_eq vary in the ranges 99.3(1)°–154.5(1)° (I); 115.2(2)°–123.3(2)° (II); 115.7(4)°–123.3(4)° 115.2(5)°–125.6(5)° (IIIa); and 107.9(4)°-129.1(4)°, 113.7(4)°-124.8(5)° (IIIb). The Sb-C and Sb-O bonds are 2.138(3)-2.176(3), 2.319(2) Å (I); 2.111(6)–2.163(5), 2.243(4) Å (II); 2.072(13)–2.169(11), 2.252(7), 2.284(7) Å (IIIa); and 2.047(11)–2.190(11), 2.224(7), 2.256(7) Å (IIIb). The intramolecular distances Sb…O=C are 2.528(3) (I); 3.267(7) (II); 3.381(7), 3.436(7) (IIIa); and 3.351(7), 3.162(7) Å (IIIb). For structures I, II, and III, the CIF files are CCDC 929151, 941542, and 941543, respectively.     

Syntheses, spectroscopic characterization and metal ion binding properties of benzo-15-crown-5 derivatives and their sodium and nickel(II) complexes

New benzo-15-crown-5 derivatives containing nitro, amine and imine groups were prepared. Nitro compound (1) was prepared after the reaction?4′,5′-bis(bromethyl)benzo-15-crown-5 and o-nitrophenol in the presence of NaOH. After reduction process by using hydrazine hydrate and Pd/C amine compound (2) was formed. New crown ether imine compounds (3–5) were synthesized by the condensation of corresponding crown ether diamine (2) with salicylaldehyde derivatives. Sodium complexes of the crown compounds (1a–5a) form crystalline 1:1 (Na⁺: ligand) complexes with sodium perchlorate. Nickel(II) complexes (3b–5b) with 1:1 (Ni²⁺:ligand) stoichiometries were also been synthesized from the Schiff bases (3–5). The results indicated that the Schiff base ligands coordinated through the azomethine nitrogen and phenolic oxygen. The extraction ability of compounds (1, 3, 4 and 5) were also evaluated in chloroform by using several alkali and transition metal picrates such as Li⁺, Na⁺, K⁺, Cr³⁺, Mn²⁺, Ni²⁺, Cu²⁺, Zn²⁺ and Pb²⁺.     

Synthesis and structural features of tris(5-bromo-2-methoxyphenyl)antimony dicarboxylates

Tris(5-bromo-2-methoxyphenyl)antimony bis(4-nitrophenylacetate) (I), tris(5-bromo-2-methoxyphenyl)antimony bis(2-methoxybenzoate) (II), and tris(5-bromo-2-methoxyphenyl)antimony bis(phenylpropiolate) (III) have been synthesized via the reaction between tris(5-bromo-2-methoxyphenyl) antimony and 4-nitrophenylacetic acid, 2-methoxybenzoic acid, and phenylpropiolic acid, respectively, in the presence of hydrogen peroxide (molar ratio: 1: 2: 1). According to X-ray diffraction data, the antimony atom in molecules of complexes I–III has a distorted trigonal bipyramidal coordination. The OSbO axial angles and the CSbC bond angles in the equatorial plane are 173.27(15)°, 172.96(11)°, 172.99(10)°, and 115.5(2)°–123.3(2)°, 108.81(16)°–129.32(17)°, and 110.66(17)°–127.91(17)°, respectively. The Sb-O bond lengths are 2.092(4) and 2.115(4)Å in I, 2.088(3) and 2.097(2) Å in II, and 2.096(3) and 2.120(3) Å in III. The Sb-C bonds range within 2.095(6)–2.123(6) Å in I, 2.107(4)–2.117(4) Å in II, and 2.097(4)–2.116(4) Å in III. Complexes I, II, and III are observed to have intramolecular Sb…OCH₃ contacts (3.169–3.226, 3.134–3.174, and 3.147–3.196 Å, respectively) in addition to Sb…O=C interactions (3.121, 3.139Å; 2.944, 3.038 A0; 3.111, 3.120 Å).     

Syntheses and spectroscopic characterization of double-armed benzo-15-crown-5 derivatives and their sodium and potassium complexes

A series of new benzo-15-crown-5 derivatives (1–6) containing formyl and imine groups were prepared. New formyl crown ethers (1 and 2) were prepared by reaction of 4′,5′-bis(bromomethyl)benzo-15-crown-5 with 2-hydroxy-3-methoxybenzaldehyde (o-vanillin) and 2-hydroxy-5-methoxybenzaldehyde in the presence of NaOH. New Schiff bases (3–6) were synthesized by the condensation of corresponding aldehydes with 1,3-diaminopropane and 1,4-diaminobutane. Sodium and potassium complexes (1a–6a and 1b–6b) of the crown compounds forming crystalline complexes of 1:1 (Na⁺:ligand) and 1:2 (K⁺:ligand) stoichiometries were also synthesized. The structures of the aldehydes 1 and 2, imines 3–6 and complexes (1a–3a and 1b–3b) were confirmed on the basis of elemental analyses, IR, ¹H- and ¹³C-NMR, and mass spectroscopy.     

Dipyrrolylquinoxaline-bridged hydrazones: a new class of chemosensors for copper(II)

Novel 2,3-bis(1H-pyrrol-2-yl)quinoxaline-functionalized hydrazones were prepared and characterized as new chemosensors for copper(II) ion. The binding properties of the compounds 4, 5, 6 and 7 for cations were examined by UV–vis, fluorescence spectroscopy, and linear sweep voltammetric experiments (LSV). The results indicate that a 1:1 stoichiometric complex is formed between compound 4 (or 5, 6, 7) and copper(II) ion, and the association constant is 1.3?×?10⁵ M^?1 for 4, 2.1?×?10⁶ M^?1 for 5, 4.1?×?10⁵ M^?1 for 6 and 8.0?×?10⁵ M^?1 for 7, respectively. The recognition mechanism between compound 4 (or 5, 6, 7) and metal ion was discussed based on their electrochemical properties, absorbance changes, and the fluorescence quenching effect when they interact with each other. Control experiments revealed that compound 4 (or 5, 6, 7) has a highly selective response to copper (II) ion.     

A novel view of modelling interactions between synthetic and biological polymers via docking

Multipoint interactions between synthetic and natural polymers provide a promising platform for many topical applications, including therapeutic blockage of virus-specific targets. Docking may become a useful tool for modelling of such interactions. However, the rigid docking cannot be correctly applied to synthetic polymers with flexible chains. The application of flexible docking to these polymers as whole macromolecule ligands is also limited by too many possible conformations. We propose to solve this problem via stepwise flexible docking. Step 1 is docking of separate polymer components: (1) backbone units (BU), multi-repeated along the chain, and (2) side groups (SG) consisting of functionally active elements (SG _F ) and bridges (SG _B ) linking SG _F with BU. At this step, probable binding sites locations and binding energies for the components are scored. Step 2 is docking of component-integrating models: [BU] _m , SG = SG _F –SG _B , BU–SG, BU–BU(SG)–BU, BU(SG)–[BU] _m –BU(SG), and [BU _var (SG _var )] _m . Every modelling level yields new information, including how the linkage of various components influences on the ligand—target contacts positioning, orientation, and binding energy in step-by-step approximation to polymeric ligand motifs. Step 3 extrapolates the docking results to real-scale macromolecules. This approach has been demonstrated by studying the interactions between hetero-SG modified anionic polymers and the N-heptad repeat region tri-helix core of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, the key mediator of HIV-1 fusion during virus entry. The docking results are compared to real polymeric compounds, acting as HIV-1 entry inhibitors in vitro. This study clarifies the optimal macromolecular design for the viral fusion inhibition and drug resistance prevention.     

Über Reaktionen mit Betainen, 18. Mitt. Über Betaine und ihre Beziehungen zu N-Yliden. Trifluoracetyl-N-methylide und ihre Beziehungen zu den entsprechenden Ammoniumbasen

The betaines1b–d were prepared⁴ by systematic variation of the alkyl groups and were reacted with trifluoroacetic acid anhydride (TFA) to give the diacyl-ylides2b,c. The betain1d andTFA afford the trifluoroacetate3d ⁵. The salts3b,c, which result from hydrolysis of2b,c as well as3d (X=I) can be transformed in 75 to 83% yield into the monoacyl-ylides4b–d with the help of silver oxide. Aqueous solutions of4a–d exhibit alkalinepH, which points to the formation of the corresponding ammonium bases. In the case of4b,c the bases5b,c could be isolated. It can be shown, that4b,c and5b,c, respectively, undergo a reversible addition or elimination of one mole wather with great ease.     

Synthesis and characterization of benzothiazol-2-one derivatives as anti-inflammatory and analgesic agents

A series of new compounds bearing a 1,3-benzothiazol-2-one nucleus have been synthesized using 5,6-dimethyl-3-(2-oxo-propyl)-1,3-benzothiazol-2-one (1) as a key starting compound. The reaction of 1 with some nucleophilic compounds led to the formation of compounds 2, 3, 4, 5a, b, 6 and 7a, b. The thiosemicarbazone derivatives 7a, b were treated with a number of halo ketones to produce the new heterocyclic compounds 9–13, while their reaction with acid anhydrides led to the formation of the derivatives 14 and 15. Also, compound 1 was condensed with different aromatic aldehydes to afford the corresponding chalcones 18–22. The structures of all the novel compounds have been determined by analytical and spectral data. Some of the compounds were selected to be evaluated as anti-inflammatory and analgesic agents.     

Watson–Crick versus imidazopyridopyrimidine base pairs: theoretical study on differences in stability and hydrogen bonding strength

Matsuda and coworkers demonstrated that imidazopyridopyrimidine nucelobases (N ^N , O ^O , N ^O , tO ^O , and O ^N ) can mimic Watson–Crick nucleobase in forming H-bonds in DNA double helix. In the present study, we address the question about the strengths of the H-bonds in imidazopyridopyrimidine base pairs compared to those in Watson–Crick ones by focusing particularly on the nature of these interactions. Optimized structures of imidazopyridopyrimidine, imidazopyridopyrimidine–Watson–Crick, and Watson–Crick base pairs are obtained at the DFTB3LYP/6-311++G (d,p). The nature and strength of the intramolecular H-bonds in these base pairs have been investigated based on natural bond orbital (NBO method) to consider the effect of charge transfer, “atoms-in-molecules” (AIM) topological parameters, and decomposition of the interaction energies using the energy decomposition analysis (EDA). These investigations imply that N ^N –O ^O and N ^O –O ^N can form base pairs with four H-bonds (most stable than those of Watson–Crick base pairs) when they incorporated into DNA double helix. Furthermore, it can be deduced that O ^N and N ^N nucleobases form energetically more favorable pairs with adenine and guanine than the normal Watson–Crick counter parts. These results can be helpful for the stabilization and regulation of a variety of new base-pairing motif of DNA structures.     

Synthesis and anti-viral activities of some 3-(naphthalen-1-ylmethylene)-5-phenylfuran-2(3H)-one candidates

3-(Naphthalen-1-ylmethylene)-5-phenylfuran-2(3H)-one 1 was prepared and converted into a variety of heterocyclic systems of synthetic and biological importance. Benzylamine was reacted with furanone 1 to afford compounds 2 and 3 according to the reaction conditions. Butanamide 2 was reacted with thionyl chloride or thiourea to give derivatives 4 and 5, respectively. Compound 3 was reacted with ethyl cyanoacetate to give the corresponding pyrrolopyridine derivative 6. Treatment of 1 with hydrazine hydrate afforded compounds 7 and 8 according to the reaction conditions. Also, compound 1 was reacted with phenyl hydrazine, hydroxyl amine, malononitrile or thiourea to give compounds 9–12, respectively. Cyclization of 7 with ethoxymethylene-malononitrile, ethyl-(ethoxymethylene)cyanoacetate, carbon disulphide or acetylacetone afforded the corresponding compounds 13–16, respectively. Condensation of 7 with p-nitrobenzaldehyde gave the corresponding hydrazone 17, which was treated with thioglycolic acid or chloroacetyl chloride to give compounds 18 and 19, respectively. Also, most of the prepared products were tested for anti-avian influenza virus and revealed promising antiviral activity against H5N1 virus [A/Chicken/Egypt/1/2006 (H5N1)] by determination of both TC ₅₀ and ED ₅₀ and confirmed by plaque reduction assay on MDCK cells. Compounds 7, 8, 11, 12 and 13 showed the highest effect compared with the other tested compounds.     

Phosphorus–nitrogen compounds: part 16. Synthesis, stereogenism, anisochronism and the relationship between 31P NMR spectral and crystallographic data of monotopic spiro-crypta phosphazene derivatives

The condensation reactions of N₂O₃-donor type coronands (1–3) with hexachlorocyclotriphosphazatriene, N₃P₃Cl₆, resulted in the formation of spiro-crypta phosphazene derivatives (4–6). These compounds with excess morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD) afford fully substituted morpholino (7 and 10) and 1,4-dioxa-8-azaspiro[4,5]deca (8)-substituted phosphazene derivatives, respectively. Whilst, in the same conditions, the reactions of 4, 5 and 6 with pyrrolidine, morpholine and DASD also produce partially pyrrolidino-substituted geminal (9 and 11), mono-substituted pyrrolidino (12), morpholino (13) and 1,4-dioxa-8-azaspiro[4,5]deca (14) phosphazenes. It has been clearly observed that the chloride replacement reactions of 4, 5 and 6 with pyrrolidine lead to the geminal products. Compounds 7, 8 and 10 are the first examples of anisochronic tetrakis (amino) phosphazenes according to ³¹P NMR data. The structures of 7, 8 and 10–14 have been determined by FTIR, MS, ¹H, ¹³C and ³¹P NMR, DEPT, and HETCOR spectral data. The solid-state structures of 9, 13 and 14 have been examined by X-ray diffraction techniques. The sums of the bond angles around the spiro cyclic nitrogen atoms [344.8(4)° and 347.6(4)°] of 9, indicate that the nitrogen atoms have pyramidal geometries. Thus, the N atoms seem to have stereogenic configurations. Compounds 12–14 also have two stereogenic P-atoms, and they are expected to be in the mixture of enantiomers. The relationships between NPN (α and α′) bond angles and δP_spiro values and the correlation of Δ(P–N) with δP_spiro and Δ(δP) values are presented.     

Phytochemical Study of the Rhizome of Pinellia ternata and Quantification of Phenylpropanoids in Commercial Pinellia Tuber by RP-LC

Four phenylpropanoids, (E)-p-coumaryl alcohol (1), 3,4-dihydroxycinnamyl alcohol (2), sachaliside 1 (3), and coniferin (4) have been isolated from the rhizome of Pinellia ternata. Their structures were elucidated by spectroscopic methods. Compounds 1–3 were isolated from the genus Pinellia for the first time. Compound 4 was isolated from this plant for the first time. A rapid, sensitive, and accurate reversed-phase high-performance liquid chromatographic method with UV detection at 260 nm was established for simultaneous separation and determination of the four phenylpropanoids in nineteen batches of dried rhizomes of P. ternata. Compounds were separated on a 250 × 4.6 mm C₁₈ column with methanol–acetonitrile–water–phosphoric acid, 20:5:75:0.3, as mobile phase. The amounts of 1–4 in the rhizome of P. ternata could be easily determined within 30 min. The linear calibration ranges for 1–4 were 0.05–137.50, 0.66–1050.00, 0.06–30.00, and 0.05–67.50 μg mL^?1, respectively. Recovery of 1–4 was 97.43–103.73%, with RSD from 0.12 to 1.62%. Limits of quantification for 1–4 were 50, 660, 60, and 50 ng mL^?1, respectively. The method was successfully used for phytochemical analysis of phenylpropanoids from the rhizome of P. ternata.     

Synthesis and molecular and crystal structures of binuclear complexes of Sm(III), Eu(III), Gd(III), Tb(III), and Dy(III) nitrates with 4,4,10,10-tetramethyl-1,3,7,9-tetraazospiro[5.5]undecane-2,8-dione

Binuclear complexes of Sm(III), Eu(III), Gd(III), Tb(III), and Dy(III) nitrates with 4,4,10,10-tetramethyl-1,3,7,9-tetraazospiro[5.5]undecane-2,8-dione (C₁₁H₂₀N₄O₂, SC)—[Sm(NO₃)₃(SC)(H₂O)]₂(I), [Eu(NO₃)₃(SC)(H₂O)]₂ (II), [Gd(NO₃)₂(SC)(H₂O)₃)]₂(NO₃)₂ (III), [Tb(NO₃)₃(SC)(H₂O)]₂ (IV), [Dy(NO₃)₃(SC)(H₂O)]₂ (V), are synthesized, and their X-ray diffraction analyses are carried out. The crystals of complexes I–V are monoclinic: space group P2₁/n for III and P2₁/c for I, II, IV, and V. In centrosymmetric coordination complexes II, III, IV, and V, the Ln atoms are coordinated by two O(1) and O(2) atoms of two molecules of the SC ligands bound by a symmetry procedure (1 ? x, ?y, 1 ? z), three bidentate nitrate anions, and a water molecule. The coordination numbers of the metal atoms are equal to 9, and the coordination polyhedra are considerably distorted three-capped trigonal prisms, whose bases include the O(1), O(2), O(12) and O(3), O(7), O(9) atoms. The dihedral angle between the bases of the prism is 18°, and that between the mean planes of the side faces is 55°–71° for I, 17° and 55°–71° for II, 16° and 55°–70° for IV, and 16° and 55°–70° for V. The Sm...Sm distance in complex I is 9.44 Å, Eu...Eu in II is 9.42 Å, Tb...Tb in IV is 9.36Å, and Dy...Dy in V is 9.36Å. The gadolinium atom in complex III is coordinated by two oxygen atoms of two ligand molecules bound by a symmetry procedure (?x, ?y + 1, ?z + 1), two bidentate nitrate anions, and three water molecules. One of the nitro groups in compound III is localized in the external coordination sphere of the metal. The coordination number of gadolinium is 9, and the coordination polyhedron is a significantly distorted three-capped trigonal prism, whose base includes the O(1), O(2), O(7) and O(4), O(5), O(9) atoms. The dihedral angle between the bases of the prism is 22.8°, and that between the mean planes of the side faces is 53°–72°. The Gd...Gd distance in complex III is 9.17 Å.     

Synthese von Pyridonen aus Enaminen und Cyanessigsäuren

Reaction of enamines1 a–e with cyanoacetic acids2 a,b in acetic anhydride at about 100°C yields the α-cyanoacetylated enamines3 a–g. Under the same conditions methyl 4-cyano-2-(2-pyridyl)-acetoacetate3 h is obtained from methyl 2-pyridylacetate and2 a. Compounds3 are cyclized in hydrochloric acid yielding the 4-hydroxy-2-pyridones4; on the other hand in ethanolic sodium ethoxide solution the 2-amino-4-pyridones are obtained. The esters5 a,b andd are saponified to give the acids7 a–c which decarboxylate at 250°C to8 a–c.     

Crescent aromatic oligothioamides as highly selective receptors for copper(Ⅱ) ion

A series of crescent aromatic oligothioamides(4, 6, 8, 15, and 18) bearing different number of sulfur atoms were designed and synthesized via thionation of their corresponding aromatic oligoamides(3, 5, and 7) using Lawesson's reagent. The X-ray structure of a trimeric analogue(13) revealed the presence of intramolecular three-center hydrogen bonds that are responsible for the rigidification of the molecular backbone. The extraction by these novel receptors toward some representative heavy metal cations(Zn2+, Cd2+, Co2+, Ni2+, Pb2+, and Cu2+) and alkali and alkaline earth metal cations(Li+, Na+, K+, Rb+, Cs+, Ca2+, and Sr2+) demonstrated high efficiency(83.5%–96.4%) and superior selectivity for Cu2+ over other selected metal cations. Particularly, the extractability was correlated to both the number of sulfur atoms and orientation of thiocarbonyl groups as revealed in the order: 6 4 18 15. This is in stark contrast to the oligoamides that only gave much lower extractability(5.9%–16.4%), suggestive of the importance of replacement of carbonyl oxygen atoms with sulfur atoms in the extraction of Cu2+. The complexation behavior of 4, 6, and 8 with Cu2+ was also examined by UV-Vis and NMR techniques.     

Synthesis of selectively deuterated and tritiated lupane derivatives with cytotoxic activity

The aim of this work was to synthesize deuterated and tritiated analogues of highly oxidized lupane derivatives known from our group. We selected compounds that previously showed very high cytotoxic activity on multiple cancer cell lines in order to further investigate the mechanism of their action. From starting material (compounds 1–4), we obtained benzyl platanate (5) and its reaction with deuteromethyltriphenylphosphonium iodide gave deuterated compound 6. Following benzyl deprotection gave free acid 7 and oxidation with SeO₂ gave 30-oxo-[29-²H₂]lup-20(29)-en-28-oic acid (8), which is one of the most active compounds synthesized in our group to date (IC₅₀ 6 μmol/L on CEM cell line). The alkylation of benzyl 2-hydroxy-3-oxolupa-1,20(29)-dien-28-oate (9) with methyliodide or deuteromethyliodide followed by a series of deprotection and hydrogenation steps gave compounds 10–14, where 2β-[31-²H₃]methoxy-3-oxolupan-20(29)-en-28-oic acid (13) is especially interesting, it showed lower activity on CEM cell line (IC₅₀ 10 μmol/L) however, it was very active against Ph1—positive human leukemia BV-173 (IC₅₀ 0.91 μmol/L) and against human myelogenous leukemia K562 (IC₅₀ 0.52 μmol/L). Selectively labelled [3α-²H] and [3α-³H] methyl 3β-acetoxy-21,22-dioxolup-18-en-28-oates 24, 25 were prepared in three steps by reduction of corresponding 3-oxo derivatives and they showed moderate activity on CEM cell line (IC₅₀ 10 μmol/L). In total, 11 labelled compounds (6–8, 11, 14, 18, 19, 21, 22, 24 and 25) have not been reported before.     

Synthesis, characterization and aggregation behaviour of novel peripherally tetra-substituted octacationic water soluble metal-free and metallophthalocyanines

In this study, a new phthalonitrile derivative 3 bearing 1,3-bis[3(dimethylamino)phenoxy]propan-2-ol 1, metal-free phthalocyanine (Pc) 4, metallophthalocyanines (MPcs) 5–7 and their quaternized derivatives 4a–7a were synthesized. Metal-free Pc 4 was prepared by cyclotetramerization of phthalonitrile derivate 3 and MPcs 5–7 were synthesized by heating 3 with NiCl₂, CoCl₂ and CuCl₂ in n-pentanol in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene, respectively. Quaternization of the dimethylamino functionality produced quaternized octacationic water soluble metal-free, Ni, Co and Cu Pcs which were soluble in water, DMF, DMSO. The aggregation behaviour of these compounds were investigated in different concentrations of chloroform for metal-free, Ni, Co and Cu Pcs. The effect of solvents on absorption spectra were studied in various organic solvents. The novel compounds were characterized using IR, ¹H-, ¹³C NMR, UV–vis and MS spectral data.