Determining binding constants for 1:1 and 1:2 inclusion complexes of ester betulin derivatives with (2-hydroxypropyl)-β-cyclodextrin by affinity capillary electrophoresis

The complexation of ester betulin derivatives with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) was studied by mobility shift affinity CE. Electrophoretic mobility for triangular peaks was calculated using the parameter a₁ of the Haarhoff–Van der Linde function instead of the peak top time. Dependences of the viscosity corrected electrophoretic mobility on HP-β-CD concentration were not described on the basis of only complexes with 1:1 stoichiometry due to the fact that these binding curves did not reach a plateau. However, the dependences were well described taking into account both 1:1 and 1:2 complexes. The presence of higher order equilibria was also revealed by x-reciprocal plots. The values of apparent binding constant logarithm, obtained for the first time, for 1:1 and 1:2 HP-β-CD complexes of betulin 3,28-diphthalate and betulin 3,28-disuccinate with 95% confidence interval limits in brackets are the same within error and are equal to 4.85 (4.73–4.95), 8.56 (7.75–8.82), 4.92 (4.86–4.97), and 8.54 (8.23–8.72) at 25°C, respectively. These values for 1:1 and 1:2 HP-β-CD complexes of betulin 3,28-disulfate at 25°C are 4.61 (4.57–4.64) and 7.11 (6.57–7.34), respectively. The binding constants for betulin 3,28-disulfate agree with the previously obtained results from the separation in the thermostatted capillary segment.     

Strong complexation of water-soluble betulin derivatives with (2-hydroxypropyl)-γ-cyclodextrin studied by affinity capillary electrophoresis

The complexation between (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD) and water-soluble betulin derivatives, betulin 3,28-disulfate (DSB) and betulin 3-acetate-28-sulfate (ASB), belonging to the class of pentacyclic lupane triterpenoids, was studied using mobility shift ACE (ms ACE). It was found that the complexation is a high-affinity interaction. In this case, a very low amount of HP-γ-CD should be added to the BGE, and triangular peaks are observed as a result of ligand deficiency in the sample zone. Le Saux et al. showed in 2005 that using the parameter a₁ of the Haarhoff-Van der Linde (HVL) function instead of the migration time measured at the peak apex eliminates the effect of ligand deficiency on effective electrophoretic mobility. Therefore, the electrophoretic mobilities of asymmetrical peaks of DSB and ASB were calculated in this way. The obtained experimental data correspond to 1:1 complexes. The calculated values of binding constants logarithms at 25°C are 6.70 ± 0.05 and 7.03 ± 0.10 for the HP-γ-CD complexes of DSB and ASB, respectively.     

Selective Oxidation of Betulin by Cr(VI) Reagents

Oxidation of betulin by pyridinium dichromate, pyridinium chlorochromate, and K₂Cr₂O₇ -H₂SO₄ in the presence of tetrabutylammonium bromide was studied. Products of regioselective C-3, C-28-, and exhaustive oxidation, 28-hydroxylup-20(29)-3-one, 3-hydroxy- and 3-oxolup-20(29)-en-28-al were obtained.     

Synthesis and cytotoxicity of 28-carboxymethoxy lupane triterpenoids. Preference of 28-O-acylation over 28-O-alkylation of betulin by ethyl bromoacetate

28-Carboxymethoxy lupane tritepenoids 3 and 4 were synthesized by alkylation of betulin with the THP protected 2-hydroxyethyl iodide followed by oxidation and reduction.Direct reaction of betulin (5) or betulone (10) with ethyl bromoacetate led to 28-O-acylation, instead of 28-O-alkylation.The targeted compounds 3 and 4 were not cytotoxic at the highest concentrationtested (75 mmol/L), suggesting that elongation of the chain length at the 28-position in both betulinic acid (1) and betulonic acid (2)was detrimental to the cytotoxicity.The acylation products 28-O-bromoacetates (8a, 8b and 11) and 28-O-methoxyacetate 13exhibited cytotoxicity against several cancer cell lines tested.     

Synthesis,crystal structures,and characterization of copper(II) carboxylate complexes incorporating 1,10-phenanthroline and bipyridine

A series of Cu(II) carboxylate complexes (carboxylate?=?2-fluorobenzoic acid (2-HFBA) or 4-fluorobenzoic acid (4-HFBA)) containing either one chelating 1,10-phenanthroline (phen) or 2,2′-bipyridine (bipy) have been synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy, and thermal analyses. In [Cu(bipy)(H₂O)(2-FBA)₂] (1), [Cu(bipy)(H₂O)(4-FBA)₂] (3), and [Cu(phen)(H₂O)(2-FBA)₂] (4), Cu is five-coordinate in a square pyramidal geometry and four-coordinate in [Cu(phen)(2-FBA)₂] (2). The four complexes are extended into 1-D chains through hydrogen-bonding and π?···?π interactions in 1 and 4, only hydrogen-bonding in 2, and π?···?π interactions in 3. These contacts lead to aggregation and supramolecular self-assembly.     

Unusual regioselective acylation of the primary hydroxy groups of β-cyclodextrin

The reaction of -cyclodextrin (1) with palmitoyl (2) and valeryl (4) chlorides in DMF or Py, unlike previously studied acetylation of 1, involves only the primary hydroxy groups of 1. The outcome of the reaction depends on the reaction conditions and the nature of the acid scavenger used (Et₃N, Prⁱ ₂NEt, PhNMe₂, Py). ¹³C NMR spectroscopy was shown to be an effective tool in determining the number and position of aliphatic carboxylic acid residues introduced into 1. A hypothesis stating that preliminary formation of a reactive inclusion complex (acid chloride1) is required for the acylation of 1 to occur is proposed and substantiated. This hypothesis provides a unified explanation for a variety of unusual facts observed in the acylation of 1 and its derivatives.     

Organic amines reduce trans-dichlorotetrakis(pyridine)cobalt(III) chloride to cobalt(II)

Summary The reaction of dichlorotetrakis(pyridine)cobalt(III) chloride. [CoCl₂(Py)₄]Cl, with alkyl- or arylamines in EtOH or i-PrOH yielded [CoCl₂(Py)₂] in all cases. This reduction of Co^III to Co^II takes place only in the presence of the amines. [CoCl₂(Py)₂] in EtOH is oxidized by Cl₂ gas and in the presence of pyridine gives [CoCl₂(Py)₄] ⁺, while in pyridine alone [CoCl₂(Py)₄] is formed.     

Copper(I) iodide–catalyzed amidation of phenylboronic acids/aryl bromides using 4-dimethylaminopyridine as ligand

An efficient one-pot synthesis of N-arylbenzamide is described via reaction of phenylboronic acid/aryl bromide with benzamide in the presence of CuI (5 mol%) as catalyst, 4-dimethylaminopyridine (20 mol%) as the ligand, and Cs₂CO₃ (2 mmol) as the base. This protocol was applied to synthesize a small library of N-arylbenzamide in high yields.     

以2-(1-吡唑基甲基)吡啶类化合物为配体的羰基钼、钨衍生物的合成及结构

合成了2-[1-(3-叔丁基)吡唑基甲基]吡啶(CH2(Py)(3-ButPz)),并研究了羰基钼(钨)与该配体及其类似物2-(1-吡唑基甲基)吡啶(CH2(Py)(Pz))和2-[1-(3,5-二甲基)吡唑基甲基]吡啶(CH2(Py)(3,5-Me2Pz))的反应,合成了6个含双齿螯合的2-(1-吡唑基甲基)吡啶类配体的四羰基金属衍生物CH2(Py)(3-ButPz)M(CO)4,CH2(Py)(Pz)M(CO)4和CH2(Py)(3,5-Me2Pz)M(CO)4(M=Mo或W)。当用SnCl4处理CH2(Py)(3,5-Me2Pz)M(CO)4时,Sn-Cl键对金属中心发生氧化加成得到2个杂双核金属有机化合物CH2(Py)(3,5-Me2Pz)M(CO)3(Cl)SnCl3。所有新化合物均通过了红外和核磁的表征,CH2(Py)(3-ButPz)W(CO)4和CH2(Py)(3,5-Me2Pz)W(CO)3(Cl)SnCl3的结构还得到了X-射线单晶衍射的确证。用循环伏安法测定了四羰基金属衍生物的电化学性质。     

2-(Prenyloxymethyl)benzoyl (POMB) as a new temporary protecting group for alcohols

The 2-(prenyloxymethyl)benzoyl (POMB) group was introduced in high yields to hydroxyl functions using the crystalline reagent, 2-(prenyloxymethyl)benzoic acid, in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). 2-(Prenyloxymethyl)benzoic acid is readily available, in two steps, from phthalide in 65% overall yield. The POMB group can be cleaved, in two steps, by treatment with 2,3-dichloro-5,6-dicyanoquinone (DDQ) followed by intramolecular lactonisation of the resulting hydroxy ester induced by a catalytic amount of Yb(OTf)₃·H₂O. The reaction conditions are compatible with the presence of a number of protecting groups such as isopropylidene, benzyl, acetyl, chloroacetyl, benzoyl, levulinoyl, Fmoc and Boc groups.     

Pyrroles from ketoximes and acetylene. 41. Some reactions of 1-vinyl-2-(2-furyl)- and-(2-thienyl)pyrroles

We have studied the reaction of 1-vinyl-2-(2-furyl)- and -(2-thienyl)pyrroles with trifluoroacetic anhydride, with hydrogen in the presence of catalysts (Raney nickel, palladium black, palladous chloride), with propargyl alcohol in electrophilic conditions [catalysis by perfluorobutyric acid in the system azoisobutyrodinitrile (AIBN)-CCl₄), and with alkane thiols with AIBN initiation. The products are novel substituted hetarylpyrroles.See [1] for Communication 40.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 337–342, March, 1991.     

Synthesis of 3β-hydroxy-20-oxo-30-norlupan-28-oic (platanic) acid and its glycosides

All available literature data on the chemical synthesis and isolation from natural sources of 3β-hydroxy-20-oxo-30-norlupan-28-oic (platanic) acid and its derivatives and their biological activity were reviewed. A one-step synthesis of platanic acid from betulin was developed. Its glycosylation by α-acetobromoglucose (ABG) catalyzed by Ag₂O in various solvents such as pyridine, CH₂Cl₂, and their mixture was studied. The optimal synthetic schemes for platanic acid monoglucosides and diglucoside were found. NMR spectra of platanic acid and its glycosides were studied.     

3,28-Bis-<Emphasis Type="Italic">O</Emphasis>-polyfluorobenzoylbetulin. Synthesis,Molecular Structure,and Cytotoxicity

Treatment of betulin with 2,3,4,5-tetrafluoro- and pentafluorobenzoyl chlorides in triethylamine afforded 3,28-bis-O-polyfluorobenzoylbetulins. According to the X-ray diffraction data, all six-membered rings in the 3,28-bis-O-pentafluorobenzoylbetulin molecule appear in a chair conformation, and the five-membered ring has an envelope conformation with the C¹⁷ atom deviating from the plane formed by the other four carbon atoms. Unlike betulin itself, the obtained bis-esters showed no cytotoxic effect on human lung adenocarcinoma cell line A549 and human glioblastoma cell line U251.     

2D LnIII(Nd/La)‐AgI Heterometallic and TmIII Homometallic Coordination Polymers Based on Pyridine Dicarboxylate ­Ligands

Two 2D 4d‐4f heterometallic coordination polymers, [LnAg(Py26DC)₂(H₂O)₃] · 3H₂O [Ln = Nd ( 1 ), La ( 2 ); H₂Py26DC = pyridine‐2,6‐dicarboxylic acid], and one 2D lanthanide homometallic coordination polymer, [Ln(Py25DC)(ox)_0.5(H₂O)₂] [Ln = Tm ( 3 ); H₂Py25DC = pyridine‐2,5‐dicarboxylic acid; ox = oxalate], were synthesized and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and single‐crystal X‐ray diffraction analysis. Both complexes 1 and 2 are isostructural and exhibit 3‐connected 2D heterometallic layer structures with the Schläfli symbol of (8² · 10), whereas complex 3 represents an extended 2D homometallic network structure with (4,4) topology.     

Bi- or trinuclear 2-iodobenzoate complexes of Znii: crystal structures and luminescence

Reactions of zinc nitrate with 2-iodobenzoic acid (2-IBA) and different pyridines result in binuclear Znⁱⁱ carboxylate complexes [Zn₂(2-IBA)₄L₂], where L = Py, 3-MePy and 3,5-Me₂Py, while in the case of 2,4,6-Me₃Py, trinuclear (2,4,6-Me₃PyH)₂[Zn₃(2-IBA)₆(OH)₂] is formed.     

Untersuchungen zur Darstellung des Phosphorsäurefluoridpyridiniumbetains,Py · PO2F (Py = Pyridin)

Studies on the Preparation of the Phosphoric Acid Fluoride Pyridinium Betaine, Py · PO₂F (Py = Pyridine) Under anhydrous reaction conditions phosphoric acid chloride betaine, Py · PO₂Cl ( I ), does not react with NaF or NaSO₂F to the corresponding fluorine compound Py · PO₂F ( II ). Reaction between AsF₃ and I gives rise to the formation of compound II which is detectable by N.M.R. In an excess of pyridine POCl₂F reacts with P₄O₁₀ to a mixture of I and II which are difficult to be separated. In a preparatively simple way II can be obtained by sulfur-oxygen exchange in liquid SO₂ starting from dithiophosphoric acid fluoride betaine Py · PS₂F.     

Synthesis and characterization of novel poly(arylene ether)s containing 1,3,4-oxadiazole units

Starting from some new 2,5-disubstituted-1,3,4-oxadiazole difluorides, synthesized by cyclocondensation of dihydrazides with 4-fluorobenzoic acid, novel poly(arylene ether)s were prepared by halo displacement polymerizations with bisphenol A in the presence of potassium carbonate. Model reactions demonstrated the unsuitableness for halo displacement reactions of the difluoride containing the SO₂ group. The synthesis and characterization of polymers are discussed and the thermal properties are compared with those of other polymers reported in literature.     

Synthesis,structures and magnetic properties of copper (II) and cobalt (II) complexes containing pyridyl-substituted nitronyl nitroxide and 3,5-dinitrobenzoate

Four new metal-radical complexes - [Cu(NIT3Py)₂(DTB)₂] 1, [Co(NIT3Py)₂(DTB)₂(CH₃OH)₂] 2, [Cu(NIT4Py)₂(DTB)₂(H₂O)₂] 3, [Co(NIT4Py)₂(DTB)₂(H₂O)₂] 4, (NIT3Py = 2-(3^′-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide], NIT4Py = 2-(4^′-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide], DTB = 3,5-dinitrobenzoic anion) have been synthesized by using transition metal ions, nitronyl nitroxide radicals as spin carriers, and incorporating 3,5-dinitrobenzoic acid (DTB) as a coligand.     

A Solvent Switch for the Stabilization of Multiple Hemiacetals on an Inorganic Platform: Role of Supramolecular Interactions

Reaction of Zn(OAc)₂ ? 2 H₂O with 2,6‐diisopropylphenyl phosphate (dippH₂) in the presence of pyridine‐4‐carboxaldehyde (Py‐4‐CHO) in methanol resulted in the isolation of a tetrameric zinc phosphate cluster [Zn(dipp)(Py‐4‐CH(OH)(OMe))]₄ ? 4 MeOH ( 1 ) with four hemiacetal moieties stabilized on the double‐4‐ring inorganic cubane cluster. The change of solvent from methanol to acetonitrile leads to the formation of [Zn(dipp)(Py‐4‐CHO)]₄ ( 2 ), in which the coordinated Py‐4‐CHO retains its aldehydic form. Dissolution of 1 in CD₃CN readily converts it to the aldehydic form and yields 2 . Similarly 2 , which exists in the aldehyde form in CD₃CN, readily converts to the hemiacetal form in CD₃OD/CH₃OH. Compound 1 is an unprecedented example in which four hemiacetals have been stabilized on a single molecule in the solid state retaining its stability in solution as revealed by its ¹H NMR spectrum in CD₃OD. The solution stability of 1 and 2 has further been confirmed by ESI‐MS studies. To generalize the stabilization of multiple hemiacetals on a single double‐four‐ring platform, pyridine‐2‐carboxaldehyde (Py‐2‐CHO) was used as the auxiliary ligand in the reaction between zinc acetate and dippH₂, leading to isolation of [Zn(dipp)(Py‐2‐CH(OH)(OMe))]₄ ( 3 ). Understandably, recrystallization of 3 from acetonitrile yields the parent aldehydic form, [Zn(dipp)(Py‐2‐CHO)]₄ ( 4 ). Single‐crystal X‐ray diffraction studies reveal that supramolecular bonding, aided by hydrogen‐bonding interactions involving the hemiacetal functionalities (C?OH, C?OMe, and C?H), are responsible for the observed stabilization. The hemiacetal/aldehyde groups in 1 and 2 readily react with p‐toluidine, 2,6‐dimethylaniline, and 4‐bromoaniline to yield the corresponding tetra‐Schiff base ligands, [Zn(dipp)(L)]₄ (L=4‐methyl‐N‐(pyridin‐4‐ylmethylidene)aniline ( 5 ), 2,6‐dimethyl‐N‐(pyridin‐4‐ylmethylene)‐aniline ( 6 ), and 4‐bromo‐N‐(pyridin‐4‐ylmethylene)aniline ( 7 )). Isolation of 5 – 7 opens up further possibilities of using 1 and 2 as new supramolecular synthons and ligands.     

Synthesis of Glycosides of Lupane-Type Triterpene Acids

A preparative synthesis of glucosides of the lupane-type triterpene acids betulinic, dihydrobetulinic, betulonic, dihydrobetulonic, and 3,20-dioxo-30-norlupan-28-oic was proposed. Glycosylation of 3-hydroxyacids by -acetobromoglucose (ABG) with Ag₂O was performed in pyridine (Py)to formglycosides at C-28, repeated glycosylation of which by these same reagents but in CH₂Cl₂ generated a glycoside bond at C-3 to form bisglucosides. 28-Glucosides of ketoacids were formed in high yields in both Py and CH₂Cl₂.