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1.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068609

RESUMO

Terpenoids with lactone moieties have been indicated to possess high bioactivity. Certain terpenoid lactones exist in nature, in plants and animals, but they can also be obtained by chemical synthesis. Terpenoids possessing lactone moieties are known for their cytotoxic, anti-inflammatory, antimicrobial, anticancer, and antimalarial activities. Moreover, one terpenoid lactone, artemisinin, is used as a drug against malaria. Because of these abilities, there is constant interest in new terpenoid lactones that are both isolated and synthesized, and their biological activities have been verified. In some cases, the activity of the terpenoid lactone is specifically connected to the lactone moiety. Recent works have revealed that new terpenoid lactones can demonstrate such functions and are thus considered to be potential active agents against many diseases.


Assuntos
Artemisininas/química , Lactonas/química , Sesquiterpenos/química , Terpenos/química , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antimaláricos/síntese química , Antimaláricos/química , Antimaláricos/uso terapêutico , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Artemisininas/síntese química , Artemisininas/uso terapêutico , Humanos , Lactonas/síntese química , Lactonas/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Sesquiterpenos/síntese química , Sesquiterpenos/uso terapêutico , Terpenos/síntese química , Terpenos/uso terapêutico
2.
Molecules ; 25(4)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32075004

RESUMO

The total synthesis of (-)-antrocin and its enantiomer are presented. Antrocin (-)-1 is an important natural product which acts as an antiproliferative agent in a metastatic breast cancer cell line (IC50: 0.6 µM). The key features of this synthesis are: (a) selective anti-addition of trimethylsilyl cyanide (TMSCN) to α,ß-unsaturated ketone; (b) resolution of (±)-7 using chiral auxiliary L-dimethyl tartrate through formation of cyclic ketal diastereomers followed by simple column chromatography separation and acid hydrolysis; (c) substrate-controlled stereoselective aldol condensation of (+)-12 with monomeric formaldehyde and pyridinium chlorochromate (PCC) oxidation for synthesis of essential lactone core in (-)-14; and (d) non-basic Lombardo olefination of the carbonyl at the final step to yield (-)-antrocin. In addition, (+)-9 cyclic ketal diastereomer was converted to (+)-antrocin with similar reaction sequences.


Assuntos
Produtos Biológicos/síntese química , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Lactonas/síntese química , Sesquiterpenos/síntese química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Cianetos/síntese química , Cianetos/química , Feminino , Humanos , Lactonas/química , Lactonas/farmacologia , Metástase Neoplásica , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Estereoisomerismo , Tartaratos/síntese química , Tartaratos/química , Compostos de Trimetilsilil/síntese química , Compostos de Trimetilsilil/química
3.
Org Biomol Chem ; 18(4): 687-693, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31903473

RESUMO

The first total synthesis of a marine natural product, exigurin, has been accomplished in 13 steps starting from (+)-menthone. The key intermediate (-)-10-epi-axisonitrile-3 was prepared by stereoselective intramolecular cyclopropanation followed by a cyclopropane ring opening reaction by the azide anion. The bioinspired Ugi reaction of (-)-10-epi-axisonitrile-3, formaldehyde, sarcosine and methanol successfully constructed the target exigurin in which its terpene and amino acid units were linked through an amide bond.


Assuntos
Produtos Biológicos/síntese química , Iminoácidos/síntese química , Sesquiterpenos/síntese química , Estereoisomerismo
4.
J Med Chem ; 63(4): 1597-1611, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-31977207

RESUMO

Herein we detail the discovery of a series of parthenolide dimers as activators of PKM2 and evaluation of their anti-GBM activities. The most promising compound 5 showed high potency to activate PKM2 with an AC50 value of 15 nM, inhibited proliferation and metastasis, and induced apoptosis of GBM cells. Compound 5 could promote tetramer formation of PKM2 and reduce nucleus translocation of PKM2 in GBM cells without influence on the expression of total PKM2, thereby inhibiting the STAT3 signal pathway in vitro and in vivo. PKM2 knockdown assay demonstrated that the anti-GBM effect of 5 mainly depended on the expression of PKM2 in vitro and in vivo. Compound 16, a prodrug of 5, markedly suppressed U118 tumor xenograft growth and reduced the weight of tumor. On the basis of these investigations, we propose that 16 might be considered as a promising lead compound for discovery of anti-GBM drugs.


Assuntos
Antineoplásicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piruvato Quinase/antagonistas & inibidores , Sesquiterpenos/uso terapêutico , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Pró-Fármacos/síntese química , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/metabolismo , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Biosci Biotechnol Biochem ; 84(4): 780-788, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31868104

RESUMO

Sesquiterpenoids are one of the most diverse groups in natural compounds with various chemical structures and bioactivities. In our previous work, we developed the chemoenzymatic oxygenation method based on the combination of Fe(II)-EDTA and ferric-chelate reductase that could synthesize (-)-rotundone, a key aroma sesquiterpenoid of black pepper. Fe(II)-EDTA catalyzed the oxygenation of sesquiterpene to sesquiterpenoid, and ferric-chelate reductase catalyzed the supply and regeneration of Fe(II)-EDTA in this system. We then investigated the effect of various Fe2+-chelates on the catalytic oxygenation of sesquiterpene and applied this system to the synthesis of odor sesquiterpenoids. We determined Fe(II)-NTA to be an efficient oxygenation catalyst by the screening approach focusing on ligand structures and coordination atoms of Fe2+-chelates. Valuable odor sesquiterpenoids such as (+)-nootkatone, (-)-isolongifolenone, and (-)-ß-caryophyllene oxide were oxygenatively synthesized from each precursor sesquiterpene by 66%, 82%, and 67% of the molar conversion rate, respectively.Abbreviations: EDTA: ethylenediaminetetraacetate; NTA: nitrilotriacetate; DTPA: diethylenetriaminepentaacetate; phen: o-phenanthroline; cyclam: 1,4,8,11-tetraazacyclotetradecane; TPA: tris(2-pyridylmethyl)amine; GlcDH: glucose dehydrogenase; HP-ß-CD: hydroxypropyl-ß-cyclodextrin.


Assuntos
FMN Redutase/metabolismo , Quelantes de Ferro/química , Oxigênio/metabolismo , Sesquiterpenos/síntese química , Catálise , Ciclodextrinas/metabolismo , Glucose 1-Desidrogenase/metabolismo , Ligantes
6.
Org Biomol Chem ; 17(45): 9703-9707, 2019 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701984

RESUMO

Parthenolide (PTL) strongly inhibits the detyrosination of microtubules and accelerates neuronal growth. In order to access cyclic ether derivatives of PTL, ring-closing metathesis (RCM) was investigated in comparison to intramolecular sulfone alkylation. Incompatibility of RCM with epoxides was found in this setting. Biological evaluation for tubulin carboxypeptidase inhibition indicated that the epoxide is crucial for parthenolide's activity.


Assuntos
Carboxipeptidases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Éter/farmacologia , Microtúbulos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Sesquiterpenos/farmacologia , Adulto , Carboxipeptidases/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Éter/síntese química , Éter/química , Humanos , Estrutura Molecular , Sesquiterpenos/síntese química , Sesquiterpenos/química , Relação Estrutura-Atividade , Tanacetum parthenium/química
7.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671644

RESUMO

Sesquiterpenoids constitute a marvelously varied group of natural products that feature a vast array of molecular architectures. Among them, the unusual bicyclo [6.3.0] undecane sesquiterpenoids are one of the most representative. To date, only approximately 42 naturally occurring compounds with this unique scaffold, which can be classified into seven different groups, have been reported. As the first-found member of each type, dactylol, asteriscanolide, dumortenol, toxicodenane C, and capillosanane S are characteristic of the four methyl groups on the five-eight-membered ring system. Only 11-hydroxyjasionone and sinuketal decorate the core with an isopropyl group. These natural products exhibit a wide range of bioactivities, including antifouling, anti-inflammatory, immune suppression, cytotoxic, antimutagenic, antiplasmodial, and antiviral activities. It was noted that some total syntheses of precapnellane-sesquiterpenoids (dactylol, poitediol, precapnelladiene), asteriscanolide, and 11-hydroxyjasionone have been achieved, because their cyclooctanoid core represents an important target for the development of synthetic strategies to prepare eight-membered ring-containing compounds. This review focuses on these natural sesquiterpenoids and their biological activities and synthesis, and aims to provide a foundation for further research of these interesting compounds.


Assuntos
Alcanos/síntese química , Alcanos/farmacologia , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologia , Alcanos/química , Vias Biossintéticas , Modelos Moleculares , Sesquiterpenos/química
8.
Biochem Biophys Res Commun ; 519(2): 309-315, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31506177

RESUMO

Jiadifenolide has been reported to have neurotrophin-like activity in primary rat cortical neurons, and also possesses neurotrophic effects in neuronal precursor cells derived from human induced pluripotent stem cells (hiPSCs), as we have previously reported. However, the molecular mechanisms by which jiadifenolide exerts its neurotrophic effects in rat and human neurons are unknown. Thus, we aimed to investigate the molecular mechanisms and pathways by which jiadifenolide promotes neurotrophic effects. Here, we found that jiadifenolide activated cellular communication network factor (CCN) signaling pathways by up-regulating mRNA level expression of CCN genes in human neuronal cells. We also found that CCN2 (also known as connective tissue growth factor, CTGF) protein promotes neurotrophic effects through activation of the p44/42 mitogen-activated protein kinase signaling pathway. This is the first discovery which links neurotrophic activity with CCN signaling.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator de Crescimento do Tecido Conjuntivo/biossíntese , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Sesquiterpenos/farmacologia , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/genética , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Sesquiterpenos/síntese química , Sesquiterpenos/química
9.
J Am Chem Soc ; 141(39): 15515-15518, 2019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31518120

RESUMO

A short, biomimetic synthesis of the fungal metabolite preuisolactone A is described. Its key steps are a purpurogallin-type (5 + 2)-cycloaddition, followed by fragmentation, vinylogous aldol addition, oxidative lactonization, and a final benzilic acid rearrangement. Our work explains why preuisolactone A has been isolated as a racemate and suggests that the natural product is not a sesquiterpenoid but a phenolic polyketide.


Assuntos
Lactonas/síntese química , Sesquiterpenos/síntese química , Produtos Biológicos/síntese química , Fungos , Lactonas/química , Modelos Moleculares , Estrutura Molecular , Sesquiterpenos/química
10.
J Am Chem Soc ; 141(34): 13295-13300, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31408328

RESUMO

Illisimonin A was isolated from Illicium simonsii and has a previously unreported tricyclic carbon framework. It displayed neuroprotective effects against oxygen-glucose deprivation-induced cell injury in SH-SY5Y cells. It incorporates a highly strained trans-pentalene ring system. We report the first synthesis of (±)-illisimonin A. Notable steps in the route include a 1,3-dioxa-2-silacyclohexene templated Diels-Alder cycloaddition and type-3 semipinacol rearrangement to generate the trans-pentalene. The final step is an iron-catalyzed C-H oxidation. The synthetic route is robust, with 94 mg of racemic material prepared in a single pass. Resolving an intermediate enabled the synthesis of natural (-)-illisimonin A. The absolute configuration of (-)-illisimonin A was revised to 1S,4S,5S,6S,7R,9R,10R based on the X-ray structure of a heavy-atom analogue.


Assuntos
Illicium/química , Fármacos Neuroprotetores/química , Sesquiterpenos/química , Catálise , Cristalografia por Raios X , Reação de Cicloadição , Frutas/química , Modelos Moleculares , Fármacos Neuroprotetores/síntese química , Sesquiterpenos/síntese química , Estereoisomerismo
11.
Angew Chem Int Ed Engl ; 58(43): 15304-15308, 2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31419367

RESUMO

Divergent and enantiospecific total syntheses of the indolosesquiterpenoids xiamycins A, C, F, H and oridamycin A have been accomplished. The syntheses, which commence from (R)-carvone, employ a key photoinduced benzannulation sequence to forge the carbazole moiety characteristic of these natural products. Late-stage diversification from a common intermediate enabled the first syntheses of xiamycins C and F, and an unexpected one-pot oxidative decarboxylation, which may prove general, led to xiamycin H. All synthetic intermediates and the natural products were tested for anti-fungal activity. Xiamycin H emerged as an inhibitor of three agriculturally relevant fungal pathogens.


Assuntos
Antifúngicos/síntese química , Luz , Sesquiterpenos/síntese química , Antifúngicos/farmacologia , Ciclização , Monoterpenos Cicloexânicos/química , Descarboxilação , Fungos Mitospóricos/efeitos dos fármacos , Oxirredução , Sesquiterpenos/farmacologia , Estereoisomerismo , Ustilago/efeitos dos fármacos
12.
J Org Chem ; 84(15): 9637-9647, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31293152

RESUMO

A step-economic biomimetic synthesis of mitchellenes B-H found in Eremophila sturtii has been achieved. Starting from the putative muurolane biological precursor, redox isomerization of the allylic alcohol gave an epimeric mixture of aldehydes, which could be used as a handle for cyclization onto the C6 position, using Bu3SnH-mediated radical cyclization or NHC-catalyzed Stetter reaction. The NHC-mediated approach was superior as the epimeric mixture underwent a dynamic kinetic resolution during the reaction, and reduction of the mixture with NaBH4 selectively formed the mitchellene ring system in 56% yield for the three steps. In the campaign to obtain the acid-starting material, two new natural products, mitchellene H and a muurolane aldehyde, were isolated. Synthetic procedures to access this family of natural products will enable further studies on their biological properties.


Assuntos
Materiais Biomiméticos/síntese química , Ácidos Carboxílicos/química , Eremophila (Planta)/química , Sesquiterpenos/síntese química , Materiais Biomiméticos/química , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular , Sesquiterpenos/química , Estereoisomerismo
13.
J Org Chem ; 84(17): 10953-10961, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31357857

RESUMO

The first total synthesis of anmindenol A is described in four steps. A notable feature of the synthetic route includes the efficient construction of the 3,10-dialkylsubstituted benzofulvene core via a stereoselective vinylogous Stork enamine aldol condensation. The strategy provided a blueprint for the practical preparation of derivatives with modifications in the C-10 alkyl substituents. The novel derivatives inhibited nitric oxide production in stimulated RAW 264.7 macrophage cells.


Assuntos
Desenho de Fármacos , Indenos/química , Indenos/síntese química , Sesquiterpenos/química , Sesquiterpenos/síntese química , Técnicas de Química Sintética
14.
Org Biomol Chem ; 17(30): 7140-7143, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31313801

RESUMO

This report features the first catalytic asymmetric total synthesis of a sesquiterpene, (+)-ar-macrocarpene (1), in 7 steps with 42.1% overall yields from commercially available inexpensive 5,5-dimethylcyclohexane 1,3-dione. This strategy relies on a key [3,3]-sigmatropic rearrangement effecting reductive transposition through allylic diazene rearrangement (ADR) in a single step from intermediate allylic alcohol (+)-12 under the Mitsunobu reaction conditions with o-nitrobenzenesulfonyl hydrazide (o-NBSH). Enantioselective reduction of α-bromo vinylogous ester 16 under the Corey-Bakshi-Shibata reduction conditions forges the required stereocenter in the allylic alcohol (+)-12 in a highly enantioenriched manner (95% ee).


Assuntos
Sesquiterpenos/síntese química , Estrutura Molecular , Sesquiterpenos/química , Estereoisomerismo
15.
J Nat Prod ; 82(6): 1576-1586, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31181922

RESUMO

Analysis of 13C NMR spectroscopic data of the phlegmarine subset of Lycopodium alkaloids revealed spectral patterns that allowed the stereochemical arrangement of the four stereogenic carbons in the decahydroquinoline core to be established. A relatively simple predictive set of chemical shift combinations is reported, providing a tool for the challenging stereochemical assignment of phlegmarine-type alkaloids. Based on the chemical shifts in their NMR spectroscopic profiles, the alkaloids huperzine K and huperzine M, formally reported as cis derivatives, were structurally reassigned as trans-decahydroquinolines. The NMR spectroscopic data for huperzine M were identical to those reported for lycoposerramine Y and, hence, also implied the configurational reassignment of the latter. The revised structures of the above alkaloids were confirmed by enantioselective total synthesis. Additionally, the synthesis of (-)-serralongamine A via a common intermediate precursor is reported.


Assuntos
Alcaloides/química , Lycopodium/química , Quinolinas/química , Sesquiterpenos/síntese química , Alcaloides/síntese química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesquiterpenos/química , Estereoisomerismo
16.
Biosci Biotechnol Biochem ; 83(10): 1875-1883, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31161886

RESUMO

(-)-Rotundone, a sesquiterpenoid that has a characteristic woody and peppery odor, is a key aroma component of spicy foodstuffs, such as black pepper and Australian Shiraz wine. (-)-Rotundone shows the lowest level of odor threshold in natural compounds and remarkably improves the quality of various fruit flavors. To develop a method for the synthesis of (-)-rotundone, we focused on non-heme Fe2+-chelates, which are biomimetic catalysts of the active center of oxygenases and enzymatic supply and regeneration of those catalysts. That is, we constructed a unique combination system composed of the oxidative synthesis of (-)-rotundone using the non-heme Fe2+-chelate catalyst, Fe(II)-EDTA, and the enzymatic supply and regeneration of Fe2+-chelate by ferric-chelate reductase, YqjH, from Escherichia coli. In addition, we improved the yield of (-)-rotundone by the application of cyclodextrin and glucose dehydrogenase to this system, and thus established a platform for efficient (-)-rotundone production.


Assuntos
FMN Redutase/química , Quelantes de Ferro/química , Odorantes , Sesquiterpenos/síntese química , Catálise , Ciclodextrinas/química , Glucose 1-Desidrogenase/química , Vinho/análise
17.
Bioorg Med Chem Lett ; 29(16): 2283-2285, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31253530

RESUMO

The effects of 14 sesquiterpene hydroquinones, including 8 marine sponge-derived avarols (1-8) and 6 semisynthetic derivatives (9-14), on lipid droplet accumulation and neutral lipid synthesis in Chinese hamster ovary (CHO) K1 cells were investigated. In intact CHO-K1 cell assays, avarol (1) markedly decreased the number and size of lipid droplets in CHO-K1 cells and exhibited the most potent inhibitory activity on the synthesis of cholesteryl ester (CE) and triglyceride (TG) with IC50 values of 5.74 and 6.80 µM, respectively. In enzyme assays, sterol O-acyltransferase (SOAT), the final enzyme involved in CE biosynthesis, and diacylglycerol acyltransferase (DGAT), the final enzyme involved in TG biosynthesis, were inhibited by 1 with IC50 values of 7.31 and 20.0 µM, respectively, which correlated well with those obtained in the intact cell assay. These results strongly suggest that 1 inhibited SOAT and DGAT activities in CHO-K1 cells, leading to a reduction in the accumulation of CE and TG in lipid droplets.


Assuntos
Lipídeos/antagonistas & inibidores , Sesquiterpenos/farmacologia , Animais , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Gotículas Lipídicas/efeitos dos fármacos , Lipídeos/síntese química , Lipídeos/química , Estrutura Molecular , Tamanho da Partícula , Poríferos , Sesquiterpenos/síntese química , Sesquiterpenos/química , Relação Estrutura-Atividade , Propriedades de Superfície
18.
Bioorg Med Chem ; 27(15): 3334-3338, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31204230

RESUMO

Cytosporolide (Cytos) A-C, isolated from the fungus Cytospora sp., have anti-microbial activity, but their molecular targets in mammalian cells are unknown. We have previously reported the total synthesis of Cytos A by biomimetic hetero-Diels-Alder reaction. In this study, to examine the novel bioactivity of Cytos, we synthesized Cytos C and measured cell growth-inhibiting activities of 7 compounds, including Cytos A and C, in several human cancer cell lines. Among these compounds, Cytos C and tetradeoxycytosporolide A (TD-Cytos A), a model compound for the synthesis of Cytos A, had anti-proliferative effects on cancer cells, and TD-Cytos A exhibited stronger activity than Cytos C. In vitro topoisomerase-mediated DNA relaxing experiments showed that TD-Cytos A inhibited the activities of topoisomerase I and II, whereas Cytos C targeted only topoisomerase I. These data suggest that the anti-proliferative activities of Cytos correlate with the inhibition of topoisomerases and implicated TD-Cytos A as a novel anti-cancer drug that suppresses the activities of topoisomerase I and II.


Assuntos
Antineoplásicos/farmacologia , DNA Topoisomerases Tipo I/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores , Sesquiterpenos/farmacologia , Inibidores da Topoisomerase/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Sesquiterpenos/síntese química , Sesquiterpenos/química , Relação Estrutura-Atividade , Inibidores da Topoisomerase/síntese química , Inibidores da Topoisomerase/química , Células Tumorais Cultivadas
19.
Bioorg Med Chem ; 27(12): 2449-2465, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30992205

RESUMO

The marine sponge Aka coralliphaga is a rich source of biologically active and structurally interesting meroterpenoids. Inspired by these natural products, we have used biosynthetic speculation to devise biomimetic syntheses of siphonodictyal B, liphagal and corallidictyals A-D from sclareolide. This work resulted in the development of new cascade reactions in the synthesis of liphagal, the reassignment of the structure of siphonodictyal B, and the realisation that corallidictyals A and B are possibly isolation artefacts.


Assuntos
Produtos Biológicos/química , Hidroquinonas/síntese química , Poríferos/química , Sesquiterpenos/síntese química , Terpenos/síntese química , Animais , Produtos Biológicos/síntese química , Biomimética , Ciclização , Diterpenos/química , Hidroquinonas/química , Oxirredução , Poríferos/metabolismo , Sesquiterpenos/química , Terpenos/química
20.
Org Lett ; 21(9): 3193-3197, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-30995050

RESUMO

An asymmetric synthesis of C14-desmethylene corialactone D is described on the basis of strategic application of a metallacycle-mediated annulative cross-coupling reaction, a Still [2,3]-Wittig rearrangement, and Morken's hydroxyl-directed diboration reaction. While representing a convenient approach to access novel compositions of matter inspired by the sesquiterpenoid natural product class (including classic natural product synthesis targets including the picrotaxanes and dendrobine), these studies have led to the discovery of natural product-inspired agents that inhibit nerve growth factor (NGF)-mediated neurite outgrowth in PC-12 cells.


Assuntos
Alcaloides/síntese química , Lactonas/síntese química , Fator de Crescimento Neural/antagonistas & inibidores , Crescimento Neuronal/efeitos dos fármacos , Sesquiterpenos/síntese química , Alcaloides/farmacologia , Animais , Lactonas/farmacologia , Células PC12 , Ratos , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade
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