RESUMO
A series of amphiphilic block copolymer (BCP) micelles based on poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) (PEG) were synthesized by a one-step reaction in the presence of tris(pentafluorophenyl)borane (BCF) as a catalyst. The structural composition of PDMS-b-PEG (PR11) and PEG-b-PDMS-b-PEG (PR12) was corroborated by FTIR, 29Si NMR, and TGA. The BCPs were assembled in an aqueous solution, obtaining micelles between 57 and 87 nm in size. PR11 exhibited a higher (2.0 g L-1) critical micelle concentration (CMC) than PR12 (1.5 g L-1) due to the short chain length. The synthesized nano micelles were used to encapsulate curcumin, which is one of three compounds of turmeric plant 'Curcuma longa' with significant biological activities, including antioxidant, chemoprotective, antibacterial, anti-inflammatory, antiviral, and anti-depressant properties. The encapsulation efficiency of curcumin was 60% for PR11 and 45% for PR12. Regarding the release study, PR11 delivered 53% curcumin after five days under acidic conditions (pH of 1.2) compared to 43% at a pH of 7.4. The degradation products of curcumin were observed under basic conditions and were more stable at acidic pH. In both situations, the release process is carried out by breaking the silyl-ether bond, allowing the release of curcumin. PR11 showed prolonged release times, so it could be used to reduce ingestion times and simultaneously work as a nanocarrier for other hydrophobic drugs.
Assuntos
Curcumina , Dimetilpolisiloxanos , Micelas , Polietilenoglicóis , Curcumina/química , Curcumina/farmacologia , Dimetilpolisiloxanos/química , Polietilenoglicóis/química , Tamanho da Partícula , Boranos/química , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Tensoativos/química , Tensoativos/síntese químicaRESUMO
BF3·Et2O-catalyzed double aldol condensation between acetylated steroid sapogenins and terephtalaldehyde led to acetylated dimeric spirostanols linked through a 1,4-dimethylidenebenzene moiety in moderate to good yields. The E configurations of the introduced double bonds were corroborated by NOE experiments. Saponification of the dimeric steroids led to the corresponding dimeric spirostanols.
Assuntos
Aldeídos/química , Benzeno/química , Boranos/química , Dimerização , Éter/química , Ácidos Ftálicos/química , Sapogeninas/química , Espirostanos/síntese química , Catálise , Técnicas de Química Sintética , Espirostanos/química , EstereoisomerismoRESUMO
The reported new anilinoquinazoline-icosahedral borane hybrids have been evaluated as glioma targeting for potential use in cancer therapy. Their anti-glioma activity depends on hybrids' lipophilicity; the most powerful compound against glioma cells, a 1,7-closo-derivative, displayed at least 3.3â times higher activity than the parent drug erlotinib. According to the cytotoxic effects on normal glia cells, the hybrids were selective for epidermal growth factor receptor (EGFR)-overexpressed tumor cells. These boron carriers could be used to enrich glioma cancer cells with boron for cancer therapy.
Assuntos
Boranos/química , Inibidores de Proteínas Quinases/química , Tiazóis/química , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Glioma/metabolismo , Glioma/patologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Concentração Inibidora 50 , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/toxicidadeRESUMO
The distribution of boron in tissue samples coming from boron neutron capture therapy protocols can be determined through the analysis of its autoradiography image on a nuclear track detector. A more precise knowledge of boron atom location on the microscopic scale can be attained by the observation of nuclear tracks superimposed on the sample image on the detector. A method to produce an "imprint" of cells cultivated on a polycarbonate detector was developed, based on the photodegradation properties of UV-C radiation on this material. Optimal conditions to generate an appropriate monolayer of Mel-J cells incubated with boronophenylalanine were found. The best images of both cells and nuclear tracks were obtained for a neutron fluence of 1013 cm-2, 6 h UV-C (254 nm) exposure, and 4 min etching time with a KOH solution. The imprint morphology was analyzed by both light and scanning electron microscopy. Similar samples, exposed to UV-A (360 nm) revealed no cellular imprinting. Etch pits were present only inside the cell imprints, indicating a preferential boron uptake (about threefold the incubation concentration). Comparative studies of boron absorption in different cell lines and in vitro evaluation of the effect of diverse boron compounds are feasible with this methodology.
Assuntos
Autorradiografia/métodos , Técnicas Citológicas/métodos , Imagem Óptica/métodos , Cimento de Policarboxilato/efeitos da radiação , Radiometria/métodos , Raios Ultravioleta , Boranos/metabolismo , Linhagem Celular Tumoral , Humanos , Fenilalanina/análogos & derivados , Fenilalanina/metabolismoRESUMO
The regioselective opening of the F ring of 22-oxo-23-spiroketals using BF3·OEt2 in acetic anhydride yielded novel cholestanic frameworks with pyranone E ring 20-23. The structures of the new derivatives of botogenin, diosgenin, hecogenin and tigogenin thus obtained were established using one and two dimensional (1)H, (13)C experiments (DEPT, COSY, HETCOR, HMBC). The X-ray diffraction analysis unequivocally confirmed the R configuration at C-23 in the starting 22-oxo-23-spiroketal 18 and the Z configuration of the C23-C24 double bond in the reaction product 20.
Assuntos
Boranos/química , Éter/química , Furanos/química , Compostos de Espiro/química , Catálise , Cristalografia por Raios X , Conformação Molecular , EstereoisomerismoRESUMO
DFT calculations suggest that O-monoacyl L-tartaric acids catalyze the asymmetric conjugate alkenylboration of enones through transition structures that are stabilized by hydrogen-bonding interactions. Formation of a five-membered acyloxyborane is proposed. The hydrogen of the free carboxy group derived from the catalyst interacts with the carbonyl group of the cyclic acyloxyborane, stabilizing the transition structure and reducing the flexibility of the system. Additional stabilizing nonclassical CH···O hydrogen-bond interactions seem to determine the observed enantioselectivity.
Assuntos
Boranos/síntese química , Cetonas/química , Tartaratos/química , Boranos/química , Catálise , Ligação de Hidrogênio , Conformação Molecular , EstereoisomerismoRESUMO
Treatment of steroid sapogenins with benzaldehyde and BF(3)·Et(2)O cleanly produces E-23(23')-benzylidenspirostanes in good yields in a reaction pathway which consists on an aldol reaction followed by a dehydration step. The obtained E-23(23')-benzylidenspirostanes can be easily converted to dinorcholanic lactones by treatment with CrO(3) in acetic acid. The synthetic sequence to dinorcholanic lactones is compatible with the presence of double bonds and carbonyl groups in the steroid framework.
Assuntos
Benzaldeídos/química , Boranos/química , Lactonas/síntese química , Sapogeninas/química , Ácido Acético/química , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
We report a facile protocol to obtain 22-substituted furostans and pseudosapogenins in high yields from (25R)- and (25S)-sapogenins. This method involves the treatment of the sapogenin with acetic-trifluoroacetic mixed anhydride and BF(3)·OEt(2) at room temperature, followed by the addition of a nucleophile (H(2)O, MeOH or KSeCN). In the case of 22-hydroxyfurostans, they can be transformed to pseudosapogenins by treatment with p-toluensulfonic acid.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Química Farmacêutica , Sapogeninas/síntese química , Espirostanos/química , Anidridos Acéticos , Antineoplásicos Fitogênicos/análise , Benzenossulfonatos/química , Boranos/química , Cianetos/química , Fluoracetatos , Espectroscopia de Ressonância Magnética , Metanol/química , Estrutura Molecular , Sapogeninas/análise , Espirostanos/análise , Estereoisomerismo , Temperatura , Ácido Trifluoracético/química , Água/químicaRESUMO
The reaction of [Cp*MoCl(4)] with an excess of LiBH(4), followed by thermolysis with tellurium powder in toluene, afforded a tricapped cubane cluster, [(Cp*Mo)(4)B(4)H(4)(µ(4)-BH)(3)] (1), which represents an unprecedented metal-rich metallaborane cluster with a cubane core containing 58 cluster valence electrons (cve) and three metal-metal bonds.
Assuntos
Boranos/química , Molibdênio/química , Compostos Organometálicos/química , Estrutura Molecular , Compostos Organometálicos/síntese químicaRESUMO
During reactions of 23-oxosapogenins and the corresponding isomeric 22-oxo-23-spiroketals with MCPBA in the presence of BF(3)·Et(2)O, equilibration occurs between the ketones. The Baeyer-Villiger type oxidation is followed by fragmentation to the dinorcholanic lactones and 3-methylbutyrolactone. The mechanistic aspects of these reactions in the 25R and 25S series are discussed.
Assuntos
Boranos/química , Cetonas/química , Esteroides/química , Catálise , Oxirredução , Sapogeninas/química , EstereoisomerismoRESUMO
This work describes the enantioselective synthesis of a new series of terpenic chiral 9-aminotetrahydroacridine analogues. Several chiral ketones were synthesized from natural monoterpenes in an optically active form and subjected to the cyclodehydration reactions with anthranilonitrile in the presence of BF(3).Et(2)O as catalyst. The 9-aminotetrahydroacridine analogues were tested as acetylcholinesterase (AChE) inhibitors. Based on qualitative structure-activity relationship some trends are suggested.
Assuntos
Acetilcolinesterase/metabolismo , Acridinas/síntese química , Acridinas/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Terpenos/química , Acridinas/química , Animais , Boranos/química , Catálise , Inibidores da Colinesterase/química , Masculino , Nitrilas/química , Ratos , Ratos Wistar , EstereoisomerismoRESUMO
A convenient, mild and highly stereoselective method for C-glycosidation (alkynylation) of D-glucal with various potassium alkynyltrifluoroborates, mediated by BF3x OEt2 and involving oxonium intermediates, preferentially provides the alpha-acetylene glycoside products with good yields.
Assuntos
Boranos/química , Boratos/química , Gluconato de Cálcio/química , Glicosídeos/síntese química , Potássio/química , Glicosídeos/química , Estereoisomerismo , Especificidade por SubstratoRESUMO
A practical and efficient procedure for the enantioselective synthesis of mexiletine analogues with use of 10% of spiroborate ester 6 as chirality transfer agent is presented. A variety of mexiletine analogues were prepared in good yield with excellent enantioselectivities (91-97% ee) from readily available starting materials. The developed methodology was also successfully applied for the synthesis of novel beta-amino ethers containing thiophenyl and pyridyl fragments.
Assuntos
Antiarrítmicos/síntese química , Éteres/síntese química , Mexiletina/síntese química , Piridinas/química , Tiofenos/química , Boranos/química , Ésteres/química , Mexiletina/análogos & derivados , Modelos Químicos , EstereoisomerismoRESUMO
The syntheses of the optically pure asymmetric hydroborating agents 1 (a, R = Ph; b, R = TMS) in both enantiomeric forms are reported. These reagents are effective for the hydroboration of cis-, trans- and trisubstituted alkenes. More significantly, they exhibit unprecedented levels of selectivity in the asymmetric hydroboration of 1,1-disubstituted alkenes (28-92% ee), a previously unanswered challenge in the nearly 50 year history of this reagent-controlled process. For example, the hydroboration of alpha-methylstyrene with 1a produces the corresponding alcohol 6f in 78% ee (cf., Ipc2BH, 5% ee). Suzuki coupling of the intermediate adducts 5 produces the nonracemic products 7 very effectively (50-84%) without loss of optical purity.
Assuntos
Álcoois/síntese química , Alcanos/síntese química , Alcenos/química , Boranos/síntese química , Alcanos/química , Boranos/química , Boroidretos/química , Modelos Moleculares , Conformação Molecular , Pseudoefedrina/análogos & derivados , Pseudoefedrina/química , EstereoisomerismoRESUMO
A detailed analysis of the course of the reaction of steroid sapogenins with NaNO(2) and BF(3).Et(2)O in acetic acid is presented and some evidences on the involved mechanism are provided. Two new products of the studied reaction were isolated and unambiguously characterized with the aid of NMR and single crystal X-ray diffraction.
Assuntos
Ácido Acético/química , Boranos/química , Óxido de Etileno/química , Sapogeninas/química , Nitrito de Sódio/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Difração de Raios XRESUMO
D003 is a new active ingredient consisting of a mixture of very long chain saturated fatty acids (C(24:0)-C(36:0)) in a definite proportion, which shows antioxidant, antiosteoporotic, antiplatelet and cholesterol-lowering effects in experimental models. Five derivatization methods for determining these fatty acids by gas chromatography (GC), using diazomethane, sulphuric acid-methanol, hydrochloric acid-methanol, boron trifluoride-methanol and N-methyl-N-trimethylsilyltrifluoroacetamide were evaluated. GC analysis was carried out using a BPX-5 wide-bore column and 1-nonadecanoic acid (C(19:0)) as internal standard. Methods were similar on account of the fatty acid content determined (84.2-86.6%). However, whereas the hydrochloric acid-methanol method needed 90 min to complete the derivatization, the other methods only required 10 min. Considering costs, speed, safety and GC response, the method using sulphuric acid-methanol was found the most appropriate for determining these fatty acids. The validation of this method: linearity over a range 40-160%, accuracy assessed through a recovery study, precision within day and inter-day, and specificity, even for samples subject to stress conditions, proved it is suitable for quality control and stability studies of the very long chain fatty acids composing this active ingredient.
Assuntos
Cromatografia Gasosa/métodos , Ácidos Graxos/análise , Ácidos Graxos/isolamento & purificação , Acetamidas , Algoritmos , Boranos/química , Diazometano/química , Ácidos Graxos/química , Fluoracetatos , Cinética , Modelos Lineares , Metanol/química , Reprodutibilidade dos Testes , Saccharum/química , Ácidos Sulfúricos/química , Fatores de Tempo , Ácido Trifluoracético/química , Compostos de Trimetilsilil/químicaRESUMO
An extensive HF, MP2, B3LYP and CCSD study of the molecular structure and normal vibrations have been performed for the HCN-BF(3) molecule. Calculations with a wide range of basis sets were classified into two groups based on the optimized N-B bond distance. The results for Group A are compared with the experimental structure of the solid phase molecules. The N-B lengths of Group A are approximately linear related to the N-B-F valence angles and also to the N-B stretching frequencies. HF/DZV calculation was used to represent the solid phase model. The N-B lengths of Group B are close to those of the gas phase molecule and both N-B-F angles and N-B sensitive frequencies have roughly the same values. Differences in the chemical bond between gaseous and solid phase HCN-BF(3) are discussed based on the calculated force constants, vibrational frequencies and potential energy distributions. Vibration mode analysis indicates that the nu(4) mode in the 600-700 cm(-1) region can be assigned to the BF(3) symmetric deformation, which shifts upon (10)B/(11)B isotopic substitution. The nu(5) mode which is insensitive to isotope substitution and changes band position with the N-B distance is assigned to the N-B bond stretching vibration.
Assuntos
Boranos/química , Cianeto de Hidrogênio/química , Modelos Químicos , Isótopos , Estrutura MolecularRESUMO
1,2-O-Isopropylidenefuranose derivatives were treated with various nucleophiles in the presence of either BF(3).OEt(2) or trimethylsilyl trifluoromethanesulfonate (TMSOTf) leading to substitution products in a regio- and stereoselective manner. In particular, nucleophilic substitution of 1,2-O-isopropylidenefuranose derivatives when treated with allyltrimethylsilane was controlled by steric and electronic factors (similar to Woerpel's stereoelectronic model). On the other hand, when 1,2-O-isopropylidenefuranose derivatives were treated with trimethylsilane, in the presence of bis-O-trimethylsilyl-5-iodouracil or bis-O-trimethylsilyl-thymidine, substitution products were generated in high regio- and stereoselectivities via an unusual nucleophilic substitution with opening of the furanose ring. Based on these results, a stereoselective method for the synthesis of neutral cyclic phosphates analogous to cAMP was developed.
Assuntos
AMP Cíclico/análogos & derivados , Nucleotídeos Cíclicos/síntese química , Ribose/análogos & derivados , Boranos/química , Éter/química , Mesilatos/química , Ribose/química , Estereoisomerismo , Compostos de Trimetilsilil/químicaRESUMO
Several 1:1, 1:2, and 2:2 complexes between BF3 and CH3OH (Met), CH3COOH (AcA), (CH3)2O (DME), (CH3CH2)2O (DEE), and (CH2)2O (EOX) have been studied using ab initio (MP2) and density functional theory (DFT) (PBE, B3LYP) methods and the 6-311++G(3df,2pd) basis set. Geometrical structures and vibrational frequencies are reported, in most cases, for the first time. A detailed comparison of the vibrational frequencies for the O...BF3 vibrational modes, as well as for the nu(OH) band in the methanol and acetic acid complexes with BF3, is performed, and the theoretical frequency shifts are compared with the available experimental information. Thermochemical properties are calculated by employing counterpoise correction to alleviate the basis set superposition error. The DFT enthalpy of complexation of the 1:1 complexes results in the order of stability (AcA)2>AcA:BF3>DEE:BF3>DME:BF3>Met:BF3>EOX:BF3>(Met)2; in contrast, MP2 shows the noticeable difference that the AcA:BF3 complex is much less stable (similar to Met:BF3). The order of stability shows that, even though acetic acid prefers dimerization to complexation with BF3, the case is exactly the opposite for methanol. In both cases, the interaction of BF3 with the dimer gives rise to very stable trimers. However, in contrast to the interaction of BF3 with the methanol dimer being stronger than that with the monomer, the interaction of BF3 with the acetic acid dimer is weaker than that with the monomer. The relative strength of the complexes, discussed in the context of BF3-catalyzed ring opening of epoxides, suggests that the effect of the catalyst in a nonprotogenic solvent should be more properly ascribed to activation of the nucleophile instead of activation of the epoxide.
Assuntos
Ácido Acético/química , Boranos/química , Compostos de Epóxi/química , Éter/química , Óxido de Etileno/química , Metanol/química , Éteres Metílicos/química , Ciclização , Modelos Moleculares , Teoria QuânticaRESUMO
[reaction: see text] Aromatic O-triisopropylsilyl ketoximes were efficiently rearranged to cyclic and acyclic aniline derivatives on reduction with BF3-ethearate/borane. The bulk of the substituents on the silicon atom, the size of the aliphatic ring, and the presence of alkoxy substituents on the aryl group all play an important role in the aniline.