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1.
J Org Chem ; 89(11): 7821-7827, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38805614

RESUMEN

Total synthesis of simonsol C has been achieved, focusing on the postdearomatization transformations. Our methodology integrates an efficient combination of dearomatization and Zn/AcOH reduction to introduce an allyl group, followed by oxo-Michael addition, to construct the 6/5/6 benzofuran skeleton. It offers a novel method for synthesizing allyl-containing quaternary carbon atoms in a straightforward manner.

2.
Bioorg Chem ; 110: 104785, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33714022

RESUMEN

Schisdilactones K-U (1-11), a series of previously unreported 16,17-secopreschisanartane-type schinortriterpenoids (SNTs), were isolated from the leaves and stems of Schisandra neglecta A. C. Smith. Their structures were mainly established through analysis of their spectroscopic data. Besides, schisdilactones K (1), O (5) and R (8) were confirmed by single-crystal X-ray crystallographic analysis, and the configurations of schisdilactones T and U (10 and 11) were elucidated via quantum chemical calculation of their NMR chemical shifts and electronic circular dichroism (ECD) spectra. Schisdilactones L-S (2-8) and U (11) were found to exhibit moderate protective activities against corticosterone-induced apoptosis of PC12 cells at 20 µM, with cell viability in the range of 62.95-66.97%.


Asunto(s)
Fármacos Neuroprotectores/farmacología , Schisandra/química , Triterpenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , China , Corticosterona/antagonistas & inhibidores , Corticosterona/farmacología , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Modelos Moleculares , Estructura Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Células PC12 , Ratas , Relación Estructura-Actividad , Tibet , Triterpenos/química , Triterpenos/aislamiento & purificación
3.
Chem Res Toxicol ; 32(10): 1965-1976, 2019 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-31468958

RESUMEN

Elemicin is a constituent of natural aromatic phenylpropanoids present in many herbs and spices. However, its potential to cause toxicity remains unclear. To examine the potential toxicity and associated mechanism, elemicin was administered to mice for 3 weeks and serum metabolites were examined. Enlarged livers were observed in elemicin-treated mice, which were accompanied by lower ratios of unsaturated- and saturated-lysophosphatidylcholines in plasma, and inhibition of stearoyl-CoA desaturase 1 (Scd1) mRNA expression in liver. Administration of the unsaturated fatty acid oleic acid reduced the toxicity of 1'-hydroxylelemicin, the primary oxidative metabolite of elemicin, while treatment with the SCD1 inhibitor A939572 potentiated its toxicity. Furthermore, the in vitro use of recombinant human CYPs and chemical inhibition of CYPs in human liver microsomes revealed that CYP1A1 and CYP1A2 were the primary CYPs responsible for elemicin bioactivation. Notably, the CYP1A2 inhibitor α-naphthoflavone could attenuate the susceptibility of mice to elemicin-induced hepatomegaly. This study revealed that metabolic activation of elemicin leads to SCD1 inhibition in liver, suggesting that upregulation of SCD1 may serve as potential intervention strategy for elemicin-induced toxicity.


Asunto(s)
Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Pirogalol/análogos & derivados , Estearoil-CoA Desaturasa/antagonistas & inhibidores , Administración Oral , Animales , Inhibidores Enzimáticos/administración & dosificación , Masculino , Metabolómica , Ratones , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Pirogalol/administración & dosificación , Pirogalol/metabolismo , Pirogalol/farmacología , Estearoil-CoA Desaturasa/metabolismo
4.
Org Biomol Chem ; 17(11): 2877-2882, 2019 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-30789160

RESUMEN

We described the chemical synthesis of a sulfated trisaccharide repeating unit of fucosylated chondroitin sulfate (FCS), which has significant anticoagulant activity. Well-functionalized monosaccharides were readily prepared, and highly efficient glycosylations using a common activator (NIS/TfOH) were also presented. The synthesized trisaccharide 4 could be used to extend oligosaccharide sequences.

5.
J Nat Prod ; 78(4): 885-95, 2015 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-25871261

RESUMEN

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of hybrid natural products sharing the mevalonate/methylerythritol phosphate and polyketide biosynthetic pathways and showing considerable structural and bioactive diversity. In a systematic phytochemical investigation of Hypericum henryi, 40 PPAP-type derivatives, including the new compounds hyphenrones G-Q, were obtained. These compounds represent 12 different structural types, including four unusual skeletons exemplified by 5, 8, 10, and 17. The 12 different core structures found are explicable in terms of their biosynthetic origin. The structure of a known PPAP, perforatumone, was revised to hyphenrone A (5) by NMR spectroscopic and biomimetic synthesis methods. Several compounds exhibited inhibitory activities against acetylcholinesterase and human tumor cell lines. This study deals with the structural diversity, function, and biogenesis of natural PPAPs.


Asunto(s)
Hypericum/química , Floroglucinol , Terpenos/química , Terpenos/aislamiento & purificación , Acetilcolinesterasa/efectos de los fármacos , Humanos , Cetonas/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Floroglucinol/análogos & derivados , Floroglucinol/química , Floroglucinol/aislamiento & purificación
6.
Org Lett ; 23(18): 7254-7258, 2021 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-34459615

RESUMEN

The concise synthesis of dysifragilones A and B and dysidavarones has been accomplished for the first time in a divergent way from a common intermediate. The synthetic route features an intramolecular reductive Heck reaction to construct the 6/5/6/6/-tetracycle of dysifragilones A and B and an intramolecular palladium-catalyzed α-arylation of a sterically hindered ketone to forge the tetracyclo[7.7.1.02,7.010,15]heptadecane core structure of dysidavarone C. The late-stage introduction of amino and ethoxy groups is effective.

7.
Chem Commun (Camb) ; 56(69): 10066-10069, 2020 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-32735006

RESUMEN

The collective total synthesis of (+)-sinensilactam A, (+)-lingzhilactone B, (+)-lingzhilactone C and (-)-lingzhiol has been accomplished from a common epoxide intermediate 9. Chemoselective epoxy opening with either an aryl or alkene moiety of styrene led to different carbon skeletons, which can be advanced to a divergent and concise total synthesis of four meroterpenoids.


Asunto(s)
Compuestos Heterocíclicos de 4 o más Anillos/síntesis química , Estireno/química , Terpenos/síntesis química , Compuestos Heterocíclicos de 4 o más Anillos/química , Estereoisomerismo , Terpenos/química
8.
Org Lett ; 22(15): 5726-5730, 2020 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-32525688

RESUMEN

Aspongdopamines A and B (1 and 2), unusual adducts composed of N-acetyldopamine and adenine were isolated from the insect Aspongopus chinensis. Compounds 1 and 2 are positional isomers both isolated as racemates. Chiral separation assisted by 14-step total synthesis and computation including vibrational circular dichroism calculations allowed us to unambiguously assign the absolute configurations of eight stereoisomers. Renal fibrosis inhibition of the stereoisomers was evaluated in TGF-ß1-induced rat kidney epithelial cells.


Asunto(s)
Adenina/síntesis química , Productos Biológicos/farmacología , Dopamina/análogos & derivados , Insectos/efectos de los fármacos , Factor de Crecimiento Transformador beta1/química , Adenina/química , Animales , Dicroismo Circular , Dopamina/síntesis química , Dopamina/química , Estructura Molecular , Ratas , Estereoisomerismo , Factor de Crecimiento Transformador beta1/metabolismo
9.
Org Lett ; 21(17): 6761-6764, 2019 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-31433660

RESUMEN

Total synthesis of (±)-cochlearol A was accomplished, which features a cis 6/6 B/D ring synthesis. A TMSOTf-promoted lactonization of tert-butoxy ketoester produced the desired lactone with quaternary carbon. The cis configuration of the B/E ring is essential for regioselective B/D ring formation. Finally, simple deprotections and transformations gave cochlearol A in 16 steps from known ethyl 4-tert-butoxyacetoacetate.

10.
J Agric Food Chem ; 67(15): 4328-4336, 2019 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-30912427

RESUMEN

Myristicin is widely distributed in spices and medicinal plants. The aim of this study was to explore the role of metabolic activation of myristicin in its potential toxicity through a metabolomic approach. The myristicin- N-acetylcysteine adduct was identified by comparing the metabolic maps of myristicin and 1'-hydroxymyristicin. The supplement of N-acetylcysteine could protect against the cytotoxicity of myristicin and 1'-hydroxymyristicin in primary mouse hepatocytes. When the depletion of intracellular N-acetylcysteine was pretreated with diethyl maleate in hepatocytes, the cytotoxicity induced by myristicin and 1'-hydroxymyristicin was deteriorated. It suggested that the N-acetylcysteine adduct resulting from myristicin bioactivation was closely associated with myristicin toxicity. Screening of human recombinant cytochrome P450s (CYPs) and treatment with CYP inhibitors revealed that CYP1A1 was mainly involved in the formation of 1'-hydroxymyristicin. Collectively, this study provided a global view of myristicin metabolism and identified the N-acetylcysteine adduct resulting from myristicin bioactivation, which could be used for understanding the mechanism of myristicin toxicity.


Asunto(s)
Compuestos de Bencilo/metabolismo , Compuestos de Bencilo/toxicidad , Dioxolanos/metabolismo , Dioxolanos/toxicidad , Hepatocitos/efectos de los fármacos , Pirogalol/análogos & derivados , Acetilcisteína/química , Acetilcisteína/metabolismo , Activación Metabólica , Derivados de Alilbenceno , Animales , Compuestos de Bencilo/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocromo P-450 CYP1A1/metabolismo , Dioxolanos/química , Hepatocitos/citología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Pirogalol/química , Pirogalol/metabolismo , Pirogalol/toxicidad
11.
J Agric Food Chem ; 67(29): 8243-8252, 2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31271289

RESUMEN

Elemicin, an alkenylbenzene constituent of natural oils of several plant species, is widely distributed in food, dietary supplements, and medicinal plants. 1'-Hydroxylation is known to cause metabolic activation of alkenylbenzenes leading to their potential toxicity. The aim of this study was to explore the relationship between elemicin metabolism and its toxicity through comparing the metabolic maps between elemicin and 1'-hydroxyelemicin. Elemicin was transformed into a reactive metabolite of 1'-hydroxyelemicin, which was subsequently conjugated with cysteine (Cys) and N-acetylcysteine (NAC). Administration of NAC could significantly ameliorate the elemicin- and 1'-hydroxyelemicin-induced cytotoxicity of HepG2 cells, while depletion of Cys with diethyl maleate (DEM) increased cytotoxicity. Recombinant human CYP screening and CYP inhibition experiments revealed that multiple CYPs, notably CYP1A1, CYP1A2, and CYP3A4, were responsible for the metabolic activation of elemicin. This study revealed that metabolic activation plays a critical role in elemicin cytotoxicity.


Asunto(s)
Pirogalol/análogos & derivados , Activación Metabólica , Biotransformación , Supervivencia Celular/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/metabolismo , Células Hep G2 , Humanos , Hidroxilación , Estructura Molecular , Pirogalol/química , Pirogalol/metabolismo , Pirogalol/toxicidad
12.
Nat Prod Bioprospect ; 8(6): 453-456, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29909523

RESUMEN

Carnosic acid was used as starting material to synthesize royleanone derivatives featured C11-C14 para quinone. The importance of C-20 group of royleanone derivatives was verified by the cytotoxicity assay of royleanonic acid, miltionone I and deoxyneocrptotanshinone. Following our synthetic route, 15 amide derivatives were synthesized and 8 compounds exhibited moderate cytotoxic activities against three human cancer lines in vitro.

13.
Nat Prod Bioprospect ; 6(3): 183-6, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27095015

RESUMEN

Catalytic asymmetric formal synthesis of (-)-Triptophenolide and (+)-Triptolide have been achieved. Key reaction involves Palladium catalyzed asymmetric conjugate addition of aryl boronic acid to 3-methyl cyclohexe-1-none to form quaternary carbon. Claisen rearrangement and subsequent aldol reaction furnished trans-decaline key intermediate, which assured a formal total synthesis of (-)-Triptophenolide and (+)-Triptolide.

14.
Chem Commun (Camb) ; 52(55): 8561-4, 2016 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-27321202

RESUMEN

Enantioselective total synthesis of (+)-Lingzhiol has been achieved. It is the first example of in tandem semipinacol rearrangement reactions, the migrated aryl group further reacting with the carbonyl oxonium electrophile to furnish a polycyclic skeleton. Our synthesis involves 13 steps and proceeds in 6% overall yield.

15.
Chem Commun (Camb) ; 51(78): 14594-6, 2015 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-26288857

RESUMEN

Concise synthesis of (±)-Lingzhiol has been achieved. The key reaction involves one-step construction of a 5/5/6/6 tetra-ring backbone of Lingzhiol via epoxy-arene cyclization.


Asunto(s)
Compuestos Epoxi/química , Terpenos/síntesis química , Ciclización , Estereoisomerismo , Terpenos/química
16.
Org Lett ; 17(24): 6062-5, 2015 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-26617269

RESUMEN

Scopariusicides A (1) and B (2), two novel immunosuppressive unsymmetrical cyclobutane derivatives, were isolated from the aerial parts of Isodon scoparius. Moreover, based on the results of phytochemical investigation, a concise stereocontrolled synthesis of scopariusicide A and its analogues with enhanced biological activities was efficiently achieved using the main diterpenoid (3) isolated from this plant as a readily available starting material. A crossed intermolecular [2 + 2] photocycloaddition and a Pd-catalyzed sp(3) C-H bond ß-arylation were used synergistically to access the highly congested unsymmetrical cyclobutane core with four contiguous stereocenters.


Asunto(s)
Ciclobutanos/síntesis química , Inmunosupresores/síntesis química , Catálisis , Cristalografía por Rayos X , Reacción de Cicloadición , Ciclobutanos/química , Ciclobutanos/farmacología , Descubrimiento de Drogas , Humanos , Inmunosupresores/química , Inmunosupresores/farmacología , Isodon/química , Conformación Molecular , Estructura Molecular , Estereoisomerismo , Linfocitos T/efectos de los fármacos
17.
Org Lett ; 16(8): 2196-9, 2014 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-24697243

RESUMEN

High contents of curcusones A and B and trace amounts of spirocurcasone exist in the roots of Jatropha curcas. Here, a one-step semisynthesis method of spirocurcasone and pyracurcasone was built, not only resulted an increased yield of spirocurcasone but also produced pyracurcasone, which exhibited greater cytotoxicity compared to curcusones A and B. The plausible mechanism of the formation of pyracurcasone was proposed, and the proposed biogenetic origin for spirocurcasone by Taglialatela-Scafati was confirmed.


Asunto(s)
Diterpenos/síntesis química , Cisplatino/farmacología , Diterpenos/química , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Células HL-60 , Humanos , Jatropha/química , Estructura Molecular , Raíces de Plantas/química , Relación Estructura-Actividad
18.
Org Lett ; 15(2): 314-7, 2013 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-23265286

RESUMEN

Scopariusins A-C (1-3), three novel rearranged ent-halimanoids with a bicycle[5.4.0]undecane ring system, two new normal ent-halimanoids (4 and 5), and a new ent-clerodanoid (6) were isolated from Isodon scoparius. Moreover, a biomimetic transformation from the ent-clerodanoid to the normal and the rearranged ent-halimane diterpenoids was successfully accomplished, which not only validated the biogenetic hypothesis in this plant but also confirmed the absolute configurations of 1 and 5.


Asunto(s)
Diterpenos/aislamiento & purificación , Isodon/química , Diterpenos/síntesis química , Diterpenos/química , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular
19.
Chem Commun (Camb) ; 48(37): 4438-40, 2012 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-22370472

RESUMEN

Przewalskone (1), an unprecedented adduct of two different terpenoid units via a hetero-Diels-Alder cycloaddition, was isolated from the roots of Salvia przewalskii. The structure and absolute configurations were elucidated by extensive analysis of NMR spectra and crystal X-ray diffractions. Compound 1 exhibited significant cytotoxicities against five human cancer lines in vitro (IC(50) 0.69-2.35 µM).


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Salvia/química , Antineoplásicos/toxicidad , Línea Celular Tumoral , Diterpenos/toxicidad , Humanos , Concentración 50 Inhibidora
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