ABSTRACT
From the methanol seed extract of Rollinia occidentalis five acetogenins were isolated, sylvaticin (1), rolliniastatin-1 (2), rolliniastatin-2 (3), motrilin (4) and desacetyluvaricin (5), and evaluated for their toxicity and nutritional alterations on Spodoptera frugiperda Smith (Lepidoptera: Noctuidae). All but one of the compounds produced more than 90% mortality on early larval instars at 50 and 100 microg per g of diet. Sylvaticin caused 15 and 60% mortality at 50 and 100 microg/g, respectively, while the methanol seed extract reached 35 and 50% at 100 and 250 microg/g, respectively. The addition of R. occidentalis methanolic seed extract (100 and 250 microg/g) and sylvaticin (100 microg/g) to the larval diet brought about significant changes to the nutritional indices in connection with larvae fed the control diet. This is the first report on the isolation of acetogenins from R. occidentalis and their insecticidal effects on S. frugiperda.
Subject(s)
Acetogenins/toxicity , Insecticides/toxicity , Plant Extracts/toxicity , Rollinia/chemistry , Animals , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Larva/drug effects , Methanol , Seeds/chemistry , Solvents , SpodopteraABSTRACT
An asymmetric total synthesis of (+)-cis-sylvaticin is described. Key steps include the use of permanganate-mediated oxidative cyclization of 1,5-dienes to synthesize the two major fragments 2 and 3 and a catalytically efficient tethered RCM to unite these THF-containing fragments. In addition, t-BuP 4 base was found to reliably promote rapid alkylation of the butenolide precursor fragment 4.
Subject(s)
Furans/chemistry , Furans/chemical synthesis , Polyenes/chemistry , 4-Butyrolactone/chemistry , Alkylation , Cyclization , Furans/pharmacology , Molecular Structure , Plants, Medicinal/chemistry , Rollinia/chemistry , StereoisomerismABSTRACT
From an Argentine collection of the tropical tree Rollinia emarginata (Annonaceae), vomifoliol, dehydrovomifoliol, blumenol C, loliolide, 7-epiloliolide, vanillin, dihydroactinolide, as well as other common plant constituents were obtained, and identified by their NMR and MS features compared with authentic samples. Antifeedant and toxic actions were exerted to the polyphagous moth Spodoptera frugiperda by the ethanol extract of the plant, at 250 ppm in the larval diet. Additionally, in greenhouse studies, a 200 ppm aqueous solution of the extract produced a post-emergency herbicidal effect on the annual weed common lambsquarter (Chenopodium album).
Subject(s)
Rollinia/chemistry , Animals , Artemia , Diet , Drug Screening Assays, Antitumor , Eating/drug effects , Ethanol , Gas Chromatography-Mass Spectrometry , Herbicides/isolation & purification , Herbicides/pharmacology , Insecticides/isolation & purification , Insecticides/pharmacology , Larva , Plant Extracts/pharmacology , Plant Extracts/toxicity , Solvents , Glycine max , SpodopteraABSTRACT
The double oxidative cyclization of dienes is a viable procedure for making complex natural products containing cis-THF units. A double deprotection/double oxidative cyclization strategy using catalytic osmium tetroxide was used to construct the bisheterocyclic core of cis-sylvaticin and ultimately confirm its structure. The natural product was then prepared by a short sequence of reactions that is exceptionally concise: the final route being just 13 linear steps and 19 chemical operations in total.
Subject(s)
Furans/chemical synthesis , Osmium/chemistry , Plant Leaves/chemistry , Plants, Medicinal/chemistry , Rollinia/chemistry , Catalysis , Cyclization , Magnetic Resonance Spectroscopy , Models, Chemical , Oxidation-Reduction , StereoisomerismABSTRACT
[structure: see text] An efficient total synthesis of the annonaceous acetogenin jimenezin was achieved. The key steps used were a highly stereoselective intramolecular allylboration to establish the tetrahydropyran ring and an intramolecular Williamson reaction to close the tetrahydrofuran ring.
Subject(s)
Furans/chemical synthesis , Pyrans/chemical synthesis , Acetogenins , Fatty Alcohols/chemistry , Furans/chemistry , Lactones/chemistry , Molecular Structure , Plants, Medicinal/chemistry , Pyrans/chemistry , Rollinia/chemistry , StereoisomerismABSTRACT
[reaction: see text] An enantioselective total synthesis of (-)-mucocin has been completed. A combination of asymmetric glycolate aldol additions and ring closing metathesis reactions were exploited to construct the C18-C34 and C7-C17 fragments. A selective cross-metathesis reaction was employed as the key step to couple two complex fragments.
Subject(s)
Lactones/chemical synthesis , Pyrans/chemical synthesis , Lactones/chemistry , Molecular Structure , Pyrans/chemistry , Rollinia/chemistry , StereoisomerismABSTRACT
An enantioselective total synthesis of the proposed structure of mucoxin (1) is described. Mucoxin, an annonaceous acetogenin isolated from bioactive leaf extracts of Rollinia mucosa, is the first acetogenin containing a hydroxylated trisubstituted tetrahydrofuran (THF) ring. This natural product is a highly potent and specific antitumor agent against MCF-7 (breast carcinoma) cell lines (ED50 = 3.7 x 10(-3) microg/mL compared to adriamycin, ED50 = 1.0 x 10(-2) microg/mL). The total synthesis described herein features two regio- and stereoselective THF ring-forming reactions. The 2,3,5-trisubstituted THF portion (C13-C17) was accessed using a highly regioselective cyclization of a methylene-interrupted epoxydiol, and the 2,5-disubstituted THF ring (C8-C12) was conveniently assembled via a 1,2-n-triol cyclization strategy. The spectral data of the synthetic material and two of its diastereomers did not match the reported data for the natural product. On the basis of detailed spectroscopic analysis of the synthesized molecule, we reason that the spectral discrepancies are due to stereochemical misassignment of the natural product.
Subject(s)
Antineoplastic Agents/chemical synthesis , Fatty Alcohols/chemical synthesis , Furans/chemical synthesis , Lactones/chemical synthesis , Acetogenins , Cyclization , Fatty Alcohols/chemistry , Lactones/chemistry , Molecular Structure , Rollinia/chemistry , Spectrum Analysis , StereoisomerismABSTRACT
[structure: see text] The first total synthesis of rollicosin, a member of a rare subgroup of Annonaceous acetogenins containing two terminal gamma-lactones, is reported. The approach features a highly regio- and stereoselective tandem ring-closing/cross-metathesis reaction for construction of the east-wing lactone and incorporation of the alkyl spacer. Establishment of the C4 stereocenter and addition of the west-wing lactone were achieved by Sharpless asymmetric dihydroxylation and enolate alkylation.
Subject(s)
Combinatorial Chemistry Techniques , Furans/chemical synthesis , Lactones/chemistry , Molecular Structure , Plants, Medicinal/chemistry , Rollinia/chemistry , StereoisomerismABSTRACT
(+)-Muconin (1), isolated from the leaves of Rollinia mucosa (Jacq.) Baill. (Annonaceae), is a sequential THF/THP-possessing acetogenin that exhibits potent and selective in vitro cytotoxicity toward pancreatic and breast tumor cell lines. In this study, a new route was established for obtaining (+)-muconin (1) starting with (-)-muricatacin (2), a compound recently synthesized via the novel alpha-C-H hydroxyalkylation and alpha'-C-H oxidation of tetrahydrofuran.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Fatty Alcohols/chemical synthesis , Furans/chemistry , Furans/chemical synthesis , Lactones/chemical synthesis , Rollinia/chemistry , Acetogenins , Alkylation , Molecular Structure , Organosilicon Compounds/chemistry , Oxidation-Reduction , Plant Leaves/chemistry , StereoisomerismABSTRACT
The enantioselective total synthesis of the annonaceous acetogenin (-)-mucocin (1) was accomplished using a triply convergent 12-step sequence (longest linear sequence) in 13.6% overall yield. This represents the first application of the temporary silicon-tethered (TST) ring-closing metathesis (RCM) cross-coupling reaction and the enantioselective alkyne/aldehyde addition to the synthesis of a complex annonaceous acetogenin. Moreover, all three fragments required for the coupling reactions are conveniently prepared in 5-6 steps from two readily available enantiomerically enriched epoxides. Finally, this synthesis stimulated the development of a new approach for the construction of 3-hydroxy-2,6-disubstituted tetrahydropyrans, using the bismuth tribromide-mediated reductive etherification reaction, which represents a motif that is prevalent in a wide range of pharmacologically significant natural products.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Lactones/chemical synthesis , Pyrans/chemical synthesis , Cyclization , Rollinia/chemistry , Silicon/chemistry , StereoisomerismABSTRACT
Rollicosin (1), a new Annonaceous acetogenin, was isolated from the unripe fruits of Rollinia mucosa. Rollicosin (1) is the first compound of this type to contain lactone moieties on both sides of the aliphatic chain and to lack either tetrahydrofuran or tetrahydropyran rings. Its structure was determined on the basis of spectroscopic analyses. This compound may serve as a new prototype molecule to develop Annonaceous acetogenins as potential antitumor agents.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Furans/isolation & purification , Lactones/isolation & purification , Plants, Medicinal/chemistry , Rollinia/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Hepatocellular , Drug Screening Assays, Antitumor , Fruit/chemistry , Furans/chemistry , Furans/pharmacology , Humans , Inhibitory Concentration 50 , Lactones/chemistry , Lactones/pharmacology , Models, Molecular , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Stereoisomerism , Structure-Activity Relationship , Taiwan , Tumor Cells, Cultured/drug effectsABSTRACT
Five annonaceous acetogenins, rolliniastatin-1 [structure: see text], rolliniastatin-2 [structure: see text], laherradurin [structure: see text], squamocin [structure: see text], annonacin [structure: see text], and rotenone as a reference, differing in their NADH oxidase inhibition activity, have been evaluated for antifeedant, insecticidal, trypanocidal and cytotoxic effects on insect, mammalian and tumor cells. All the test compounds were toxic to Leptinotarsa decemlineata, demonstrated selective cytotoxicity to insect Sf9 cells and a panel of tumor cell lines with the multidrug-resistant SW480 (P-glycoprotein+, Pgp+) being the most sensitive one. Compounds [structure: see text] and rotenone had post-ingestive effects against Spodoptera littoralis larvae while [structure: see text] and rotenone were active against Trypanosoma cruzi. Based on their biochemical properties (inhibition of the mitochondrial NADH oxidase activity), the in vivo effects of these compounds on S. littoralis and their cytotoxic effects on Sf9 and tumor cells were more predictable than their effect on T. cruzi and mammalian cells.