RESUMO
Aiming to obtain the more effective pathogen inhibitive ingredients and explore the influence of introducing different heterocyclic units to carvacrol and thymol esters, twenty ester derivatives with different heterocyclic units were synthesized. And the in vitro antifungal activity of title compounds against five plant pathogenic fungi was evaluated by mycelium growth rate method. The results showed that some carvacrol and thymol esters showed good to excellent antifungal activity, and compound 9d (4-bromo-5-isopropyl-2-methylphenyl picolinate) exhibited a broad antifungal spectrum. Preliminary study indicated that the introduction of furan, thiophene and pyridine unit could enhance the antifungal activity of carvacrol and thymol esters against Botrytis cinerea and a bromine atom on the para position of benzene moiety could enhance their antifungal activity.
Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Monoterpenos/química , Timol/química , Botrytis/efeitos dos fármacos , Botrytis/patogenicidade , Ácidos Carboxílicos/química , Cimenos , Avaliação Pré-Clínica de Medicamentos/métodos , Ésteres/química , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Testes de Sensibilidade Microbiana , Monoterpenos/síntese química , Monoterpenos/farmacologia , Micélio/efeitos dos fármacos , Relação Estrutura-Atividade , Timol/síntese químicaRESUMO
A chemoenzymatic approach providing access to all four intermediates in the peppermint biosynthetic pathway between limonene and menthone/isomenthone, including noncommercially available intermediates (-)- trans-isopiperitenol (2), (-)-isopiperitenone (3), and (+)- cis-isopulegone (4), is described. Oxidation of (+)-isopulegol (13) followed by enolate selenation and oxidative elimination steps provides (-)-isopiperitenone (3). A chemical reduction and separation route from (3) provides both native (-)- trans-isopiperitenol (2) and isomer (-)- cis-isopiperitenol (18), while enzymatic conjugate reduction of (-)-isopiperitenone (3) with IPR [(-)-isopiperitenone reductase)] provides (+)- cis-isopulegone (4). This undergoes facile base-mediated chemical epimerization to (+)-pulegone (5), which is subsequently shown to be a substrate for NtDBR ( Nicotiana tabacum double-bond reductase) to afford (-)-menthone (7) and (+)-isomenthone (8).
Assuntos
Monoterpenos/síntese química , Óleos de Plantas/síntese química , Isomerismo , Mentha piperitaRESUMO
Based on the anticancer mechanism of biological alkylating agent, we designed and synthesized two alpha pinene derivatives:(1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl benzenesulfonate and (1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl 4-methylbenzenesulfonate, of which structures were confirmed by ¹H-NMR, HPLC and MS date. These two compounds showed a good inhibition of tumor cells' proliferation. Further, the computer siuulation of molecular docking and metabolic kinetics indicated that these two copounds may have stable molecular complexation with protein CDK2, which closely related to the cell cycle.
Assuntos
Antineoplásicos/síntese química , Desenho de Fármacos , Monoterpenos/síntese química , Antineoplásicos/farmacologia , Monoterpenos Bicíclicos , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Simulação de Acoplamento Molecular , Monoterpenos/farmacologia , Relação Estrutura-AtividadeRESUMO
(-)-Incarvillateine (INCA) is the major antinociceptive component of Incarvillea sinensis, which has been used to treat rheumatism and relieve pain in traditional Chinese medicine. We have developed a concise and general synthetic approach for INCA, which enabled gram-scale asymmetric syntheses of (-)-INCA, (-)-incarvilline, (-)-isoincarvilline, and six other INCA analogues. The synthesis of isoincarvilline was reported for the first time. Three structurally simplified analogues of INCA were also synthesized. In vivo screening found that INCA and two structurally optimized analogues were efficacious in preventing the acetic acid-induced writhing response. Moreover, their analgesic efficacy was demonstrated in formalin induced pain model. More importantly, administration of 20 or 40 mg/kg INCA and two structurally optimized analogues showed strong analgesic effects in spared nerve injury (SNI) model, and their effective doses were lower than the current gold standard, gabapentin (100 mg/kg in this model).
Assuntos
Alcaloides/síntese química , Alcaloides/farmacologia , Monoterpenos/síntese química , Monoterpenos/farmacologia , Neuralgia/tratamento farmacológico , Alcaloides/uso terapêutico , Animais , Descoberta de Drogas , Masculino , Camundongos , Camundongos Endogâmicos ICR , Monoterpenos/uso terapêutico , Relação Estrutura-AtividadeRESUMO
We here describe a comprehensive study on the preparation of the intensive flavor 3,9-epoxy-p-mentha-1,4(8)-diene (1). Key steps of the presented synthesis are the selective addition of MeLi to the keto-ester 7, the regioselective cyclization of the obtained triol to give the ethers 4 and 8 and the selective dehydration of ether 4 through the use of POCI3 and pyridine. It is worth noting that the presented synthesis represents the first expedient and reliable entry to ether 1. Being present in linden honey, 1 is also known as linden ether and it has been regarded as a potential marker for the authentication of the linden honey origin. Therefore, ether 1 can be used as a useful reference standard for the analysis of the natural flavors, as we demonstrated by means of its identification in a sample ofunifloral linden honey.
Assuntos
Monoterpenos/síntese química , Tilia/química , Mel/análise , Monoterpenos/análiseRESUMO
Conjugated acid derivatives containing nitrogen have been synthesized from the simple acyclic monoterpene citral, using various reactions, including Wittig, Baylis Hillman, amide and ester condensations. Similarly, amine peroxides were synthesized by subjecting citral to Mannich type reaction with amines and t-butyl hydroperoxide. Molecules 3-10 were evaluated for antimalarial activity against erythrocytic stages of chloroquine sensitive P. falciparum strain 3D7. Four derivatives displayed interesting activity with an IC50< 2.5 microM, and warrant further investigations.
Assuntos
Antimaláricos/análise , Monoterpenos/síntese química , Monoterpenos Acíclicos , Antimaláricos/síntese química , Humanos , Testes de Sensibilidade Microbiana , Monoterpenos/químicaRESUMO
A series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. The antiviral activity against HSV-1 and influenza virus H3N2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (CPE) inhibition assay in vitro. Compounds M2, M4, M5 and M34 showed higher inhibitory activity against HSV-1 virus with the TC50 values being in micromole. Compounds M28, M33, and M35 showed higher inhibitory activity against influenza virus H3N2 with their TC50 values being 96.4, 71.0 and 75.4 µM, respectively. Preliminary biological activity evaluation indicated that the anti-H3N2 and anti-HSV-1 activities improved obviously through the introduction of halogen into the structure of schizonepetin.
Assuntos
Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Monoterpenos/farmacologia , Aciclovir/farmacologia , Acilação , Animais , Antivirais/síntese química , Chlorocebus aethiops , Cães , Avaliação Pré-Clínica de Medicamentos , Esterificação , Concentração Inibidora 50 , Células Madin Darby de Rim Canino , Monoterpenos/síntese química , Células VeroRESUMO
Transient receptor potential (TRP) channels represent interesting molecular target structures involved in a number of different physiological and pathophysiological systems. In particular, TRPA1 channel is involved in nociception and in sensory perception of many pungent chemesthetic compounds, which are widespread in spices and food plants, including Perilla frutescens. A natural compound from P. frutescens (isoegomaketone) and 16 synthetic derivatives of perillaketone have been prepared and tested in vitro on rTRPA1 expressed in HEK293 cells and their potency, efficacy and desensibilisation activity measured. Most derivatives proved to be high potency agonists of TRPA1, with a potency higher than most natural agonists reported in the literature. These furylketones derivatives, represent a new class of chemical structures active on TRPA1 with many potential applications in the agrifood and pharmaceutical industry.
Assuntos
Monoterpenos/química , Perilla/química , Extratos Vegetais/química , Canais de Potencial de Receptor Transitório/agonistas , Animais , Células HEK293 , Humanos , Cinética , Estrutura Molecular , Monoterpenos/síntese química , Extratos Vegetais/síntese química , Ratos , Canais de Potencial de Receptor Transitório/químicaRESUMO
Enzymes can be used in nonpolar reaction media to modify water-insoluble substrates. A variety of pretreatments, applied to the enzyme prior to introduction to the nonpolar media, can improve enzyme activity. However, the various pretreatments have not been studied using directly comparable conditions, nor have they been applied simultaneously to test for interactive effects. This work evaluates pretreatment of lipase with various classes of additives. The pretreated lipase is used to catalyze esterification between citronellol and acetic acid in a medium of n-hexane. The effectiveness of a particular pretreatment is presented in terms of relative performance (RP), which is equal to the number of times faster the pretreated lipase catalyzes the reaction relative to untreated lipase. The individual and interactive effects of the pretreatment factors were studied and compared. Buffer salts had a much stronger performance-enhancing effect than nonbuffer salts; pretreatment with 90% (w/w) sodium phosphate yielded lipase with an RP of approx 64. A strong interaction was found between the treatments with sodium phosphate and pH adjustment. These treatments may mitigate the inhibitory effect of acetic acid. Activating effects of phase interfaces and active-site protectants are shown to be complementary to other treatments, demonstrating that they likely act by distinct mechanisms.
Assuntos
Hexanos/química , Lipase/química , Rhizomucor/enzimologia , Ácido Acético/síntese química , Ácido Acético/química , Monoterpenos Acíclicos , Sítios de Ligação , Catálise , Ativação Enzimática , Estudos de Avaliação como Assunto , Concentração de Íons de Hidrogênio , Monoterpenos/síntese química , Monoterpenos/química , Fosfatos/química , Propriedades de Superfície , Água/químicaRESUMO
A biogenetic-type synthesis of (+)-cymbodiacetal (1), a novel bismonoterpenoid dihemiacetal, is described.