Doxycycline, a tetracyclic antibiotic. Mirtazapine, a tetracyclic antidepressant. Tetracyclics are chemical compounds that contain four interconnected rings of atoms, e.g. Tröger's base.
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Ciclopramine is a tetracyclic antidepressant (TeCA) that was never marketed.
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Furthermore, lithium aluminium hydride reduction of hydrofuramide yields furfurin, a tetracyclic compound.
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Oxidative cleavage of the double bond of this intermediate would result in the loss of the terminal three carbons producing the C-17 tetracyclic enone acid unit. An N-acyltransferase reaction of tetracyclic enone and aminobenzoic acid would lead to platensimycin.
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Losindole (BI-27,062) is an antidepressant with a tetracyclic structure. It was never marketed.
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They have various pharmaceutical uses, for instance the tetracycline antibiotics and the tetracyclic antidepressants.
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SSRI (e.g. paroxetine), tricyclic antidepressants (e.g. amitriptyline), tetracyclic antidepressants (e.g. mirtazapine) and atypical antipsychotics (e.g.
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Its systematic name, 4,10-dinitro-2,6,8,12-tetraoxa-4,10-diazatetracyclo[5.5.0.05,9.03,11]-dodecane derives from its tetracyclic structure.
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Taxinine M is a tetracyclic taxane isolate derived from Taxus brevifolia, Taxus chinensis, and Taxus mairei.
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It has been reported to produce auroglaucin, bisanthrons, dihydroauroglaucin, echinulins, erythroglaucin, flavoglaucin, isoechinulins, neoechinulins, physcion, tetracyclic, and tetrahydroauroglaucin.
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Visual representation of the synthesis of Gambierol. The tetracyclic acetic acid and tetracyclic alcohol together, form the octacyclic backbone of gambierol. Stille coupling of compound 8 to dienyl stannane (9) results in the active, toxic form of gambierol.Reaction conditions: (a) Dimethyldioxirane, CH2Cl2, -78 to 0 °C; DIBAL, CH2Cl2, 90% (10:1 mixture).
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Poriferastane or 24S-ethylcholestane is a tetracyclic triterpene and the parent structure of a series of steroids, such as poriferastanol.
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Euphane is a tetracyclic triterpene that is the 13α,14β-stereoisomer of lanostane. Its derivatives are widely distributed in many plants.
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The condition is often managed with drugs including H1-antihistamines, tricyclic antidepressants, tetracyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, or benzodiazepines.
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Azipramine (TQ-86) is a tetracyclic antidepressant (TeCA) which was synthesized and assayed pharmacologically in animals in 1976, but was never marketed.
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Protostane is a tetracyclic triterpene, its natural distribution is primarily limited to the genus Alisma. It is named of considered to be the "prototype" of steroids.
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Lanosterol is a tetracyclic triterpenoid and is the compound from which all animal and fungal steroids are derived. By contrast plant steroids are produced via cycloartenol.
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The nomenclature for paclitaxel is structured on a tetracyclic 17-atom skeleton. There are a total of 11 stereocenters. The active stereoisomer is (−)-paclitaxel (shown here).
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Campestane or 24R-methylcholestane is a tetracyclic triterpene. Its derivative Campesterol (Campest-5-en-3β-ol) was first isolated from the rapeseed (Brassica campestris), hence the name.
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In prokaryotes, biosynthetic pathways exist for the tetracyclic steroid framework (e.g. in mycobacteria) – where its origin from eukaryotes is conjectured – and the more-common pentacyclic triterpinoid hopanoid framework.
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Setiptiline has a tetracyclic structure and is a close analogue of mianserin and mirtazapine, with setiptiline being delta(13b,4a),4a-carba-mianserin, and mirtazapine being 6-azamianserin.
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Biosynthesitic studies show that the benzoic ring is produced from pyruvate and acetate via the TCA cycle, while the C-17 tetracyclic enone acid core is produced from the non-mevalonate terpenoid pathway. The tetracyclic enone isotope labeling pattern observed is consistent with the biosynthesis of the tetracycle via the non-mevalonate terpenoid pathway.S W. White, J. Zheng, Y X M. Zhang, and C O. Rock, Annu. Rev. Biochem. 2005, 74, 791-831.
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Other scientists have proposed that squalene-hopene and oxidosqualene cyclases diverged from a common ancestor, a putative bacterial cyclase that would have made a tricyclic malabaricanoid or tetracyclic dammarinoid product.
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Aspergillus species on the stored products. Mycological Papers. 161:1-188 It has been reported to produce asperentins, asperflavin, auroglaucin, a bisanthron, dihydroauroglaucin, echinulins, flavoglaucin, neoechinulins, questin, questinol, tetracyclic, and tetrahydroauroglaucin.
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Reisman received a B.A. in Chemistry from Connecticut College in 2001, conducting research in the lab of Prof. Timo V. Ovaska on the synthesis of tetracyclic terpenoid natural products, including phorbol.
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Many tricyclic antidepressants, tetracyclic antidepressants, antipsychotics, ergolines, and some piperazines like buspirone, trazodone, nefazodone, etoperidone, and mepiprazole antagonize α1-adrenergic receptors as well, which contributes to their side effects such as orthostatic hypotension.
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Gray, Diane, and Timothy Gallagher. "A Flexible Strategy for the Synthesis of Tri- and Tetracyclic Lupin Alkaloids: Synthesis of ( )-Cytisine, (±)-Anagyrine, and (±)-Thermopsine." Angewandte Chemie International Edition 45.15 (2006): 2419-423. Web.
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Aspergillus, Penicillium and Talaromyces isolated from house dust samples collected around the world. Studies in Mycology. 78:63-139 It has been reported to produce auroglaucin, bisanthrons, dihydroauroglaucin, echinulins, flavoglaucin, physcion, tetracyclic, and tetrahydroauroglaucin.
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Aphidocolin is a fungus-derived tetracyclic diterpenoid that acts as a selective inhibitor for DNA polymerase α. This enzyme is necessary for replicative DNA synthesis, but does not disrupt DNA repair synthesis or mitochondrial DNA replication.
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Aspergillus cibarius sp. nov., from traditional meju in Korea. The Journal of Microbiology. 50(4):712-714 It has been reported to produce asperflavin, auroglaucin, bisanthrons, dihydroauroglaucin, echinulins, emodin, erythroglaucin, flavoglaucin, neoechinulins physcion, tetracyclic, and tetrahydroauroglaucin.
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Additional notes on species of Aspergillus, Eurotium and Emericella from Egyptian desert soil. Antonie van Leeuwenhoek. 41(3):343-351 It has been reported to produce bisanthrons, dihydroauroglaucin, echinulins, erythroglaucin, isoechinulins, neoechinulins, physcion, sulochrin, and tetracyclic.
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Taxonomische und physiologische Untersuchungen uber die Gattung Eurotium Link. ex Fr. Sydowia. 28:1-49 It has been reported to produce asperflavin, auroglaucin, bisanthrons, dihydroauroglaucin, echinulins, emodin, erythroglaucin, flavoglaucin, isoechinulins, neoechinulins, physcion, questin, questinol, tetracyclic, and tetrahydroauroglaucin.
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Setiptiline (brand name Tecipul), also known as teciptiline, is a tetracyclic antidepressant (TeCA) which acts as a noradrenergic and specific serotonergic antidepressant (NaSSA). It was launched in 1989 for the treatment of depression in Japan by Mochida.
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Oxaprotiline (developmental code name C 49-802 BDA), also known as hydroxymaprotiline, is a norepinephrine reuptake inhibitor of the tetracyclic antidepressant (TeCA) family that is related to maprotiline. Though investigated as an antidepressant, it was never marketed.
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Animal studies have shown sedative hypnotic drugs tend to show dependency in animals, but benzoctamine has been shown to not be addictive. Other animal studies also point to the drug as a possible mechanism by which to reduce blood pressure through the adrenergic system. Chemically, benzoctamine belongs to the class of compounds called dibenzobicyclo-octodienes. It is a tetracyclic compound, consisting of four rings in a three dimensional configuration, and is very closely related structurally to the tetracyclic antidepressant (TeCA) maprotiline, differing only in the length of their side chain.
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It is unclear if use during pregnancy is safe. How it works is not clear, but it may involve blocking certain adrenergic and serotonin receptors. Chemically, it is a tetracyclic antidepressant (TeCA). It also has strong antihistamine effects.
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The species of the genus Codon are annual to perennial herbs. The whole plants are densely covered with strong mineralised, unicellular trichomes on cystolithic foot- cells. The plants are growing from strong taproots. The flowers are tetracyclic and polymerous.
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The Aspergillus glaucus group. U.S. Department of Agriculture Miscellaneous Publications. 426:1-46 It has been reported to produce asperflavin, auroglaucin, bisanthrons, dihydroauroglaucin, echinulins, emodin, erythroglaucin, flavoglaucin, mycophenolic acid (tentatively identified), neoechinulins, physcion, questin, questinol, siderin, tetracyclic, and tetrahydroauroglaucin.
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Protopanaxatriol (PPT) is an organic compound characterizing a group of ginsenosides.Ginsenosides of the protopanaxatriol group cause endothelium- dependent relaxation in the rat aorta It is a dammarane-type tetracyclic triterpene sapogenins found in ginseng (Panax ginseng) and in notoginseng (Panax pseudoginseng).
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Asenapine, sold under the brand name Sycrest among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder. It was chemically derived via altering the chemical structure of the tetracyclic (atypical) antidepressant, mianserin.
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Trametes versicolor contains polysaccharides under basic research, including the protein-bound PSP and β-1,3 and β-1,4 glucans. The lipid fraction contains the lanostane-type tetracyclic triterpenoid sterol ergosta-7,22,dien-3β-ol as well as fungisterol and β-sitosterol.
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Aspergillus cumulatus sp. nov., from rice straw and air for meju fermentation. Journal of Microbiology and Biotechnology. 24(3):334-336 It has been reported to produce auroglaucin, bisanthrons, dihydroauroglaucin, echinulins, emodin, erythroglaucin, flavoglaucin, isoechinulins, neoechinulins, physcion, tetracyclic, and tetrahydroauroglaucin.
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Aspergillus mallochii is a species of fungus in the genus Aspergillus. It is from the Aspergillus section. The species was first described in 2017. It has been reported to produce auroglaucin, dihydroauroglaucin, echinulins, erythroglaucin, flavoglaucin, isoechinulins, neoechinulins, tetracyclic, and tetrahydroauroglaucin.
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The process of elongating the polypeptide skeleton occurs through a series of Claisen-like decarboxylation reactions until the linear tetracyclic skeleton is formed. Thus, minimal PKS's form a completed amidated polyketide backbone without any additional post- synthase tailoring enzymes (Figure 1). center Following the formation of the linear tetracyclic skeleton, four successive cyclization reactions must occur in a regioselective manner to produce the aromatic natural product known as pretetramid - a common precursor to both oxytetracycline and other tetracycline antibiotics. In the oxytetracycline gene cluster, these enzymes are encoded as OxyK (aromatase), OxyN (cyclase), and OxyI (cyclase).
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24-Norcholestane is a tetracyclic compound, with 20R,5α(H),14α(H),17α(H) stereochemistry, derived from steroids or sterols. It consists of three 6-membered rings and one 5-membered ring, with carbon 24 removed from the side chain off of C17.
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Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their chemical structure, which contains four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.
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Chemical structure of 12-O-tetradecanoylphorbol-13-acetate, a phorbol ester Phorbol esters are a class of chemical compounds found in a variety of plants, particularly in the families Euphorbiaceae and Thymelaeaceae. Chemically, they are ester derivatives of the tetracyclic diterpenoid phorbol.
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Die Gattung Aspergillus. neue Spezies. Diagnosen. Synonyme. Annales Mycologici. 27(3-4):205-240 It has been reported to produce asperentins, asperflavin, auroglaucin, bisanthrons, dihydroauroglaucin, echinulins, erythroglaucin, 6-farnesyl-5,7-dihydroxy-4-methylphthalide, flavoglaucin, isoechinulins, mycophenolic acid, neoechinulins, physcion, questin, questinol, tetracyclic, and tetrahydroauroglaucin.
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The main limitation of such approach, however, is the need to use constrained dienes, such as furan and cyclopentadiene. In 2009 Buszek and co-workers synthesized herbindole A using aryne [4+2]-cycloaddition. 6,7-indolyne undergoes [4+2] cycloaddition with cyclopentadiene to afford complex tetracyclic product.
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Espèces nouvelles observées au Laboratoire de Pathologie végétale. Bulletin de la Société Mycologique de France. 9:184 It has been reported to produce asperflavin, asperentins, auroglaucin, bisanthrons, dihydroauroglaucin, echinulins, 5-farnesyl-5,7-dihydroxy-4-methylphthalide, erythroglaucin, flavoglaucin, isoechinulins, mycophenolic acid, neoechinulins, physcion, questin, tetracyclic, and tetrahydroauroglaucin.
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Panaxatriol is an organic compound characterizing a group of ginsenosides.Ginsenosides of the protopanaxatriol group cause endothelium- dependent relaxation in the rat aorta It is a dammarane-type tetracyclic triterpene sapogenin found in ginseng (Panax ginseng) and in notoginseng (Panax pseudoginseng). It is formed by the dehydration of protopanaxatriol.
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Ergostane is a tetracyclic triterpene, also known as 24S-methylcholestane. The compound itself has no known uses; however various functionalized analogues are produced by plants and animals. The most important of these are the heavily derivatised withanolides. However simpler forms do exist, such as the sterane campestane (24R-methylcholestane).
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The Aspergilli. :1-272 It has been isolated from coffee beans in the UK, tea and soil in China, and malt dust in the Czech Republic. It has been reported to produce auroglaucin, bisanthrons, catenarin, dihydroauroglaucin, echinulins, epiheveadrides, erythroglaucin, flavoglaucin, isoechinulins, neoechinulins, physcion, questin, questinol, tetracyclic, and tetrahydroauroglaucin.
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Aspergillus megasporus is a species of fungus in the genus Aspergillus. It is from the Aspergillus section. The species was first described in 2017. It has been reported to produce asperflavin, auroglaucin, bisanthrons, dihydroauroglaucin, echinulin, emodin, erythroglaucin, flavoglaucin, isoechinulins, neoechinulins, preechinulin, physcion, quinolactacin (A1, A2, B), tetracyclic, and tetrahydroauroglaucin.
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It was synthesized under the hypothesis that a polyanionic cyclization (double Michael addition followed by aldol condensation) would allow access to a tetracyclic intermediate with the desired functionality. The figure below shows the key steps in the synthesis of ouabain. Key steps in the synthesis of ouabain.Deslongchamps, P. et al.
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Amoxapine, sold under the brand name Asendin among others, is a tetracyclic antidepressant (TeCA). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 years after most of the other TCAs were introduced in the United States).
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Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings. It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine. Analogues of mirtazapine include mianserin, setiptiline, and aptazapine.
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Suggested active residues in squalene-hopene cyclase During the formation of rings A through D, there is very little conformational change. The reaction therefore requires no intermediate and can take place in one step. However, ring E formation is hindered by an entropic barrier, which may explain its absence in the tetracyclic steroids.
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Another common case is the tetracyclic flower, which contains only one whorl of stamens, and therefore only four whorls in total. Tricyclic flowers also occur, generally where there is a single undifferentiated perianth. Flowers with more than five whorls are also not uncommon. The greatest variation occurs in the calyx and the androecium.
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Kametani, T.; Ogasawara, K. J. J. Chem. Soc., C 1967, 2208 center The synthesis of the tetracyclic meroterpenoid (+)-liphagal involved an aryne intermediate. Their approach employed an aryne cyclization to close the final ring of the natural product. center Multicomponent reactions of arynes are powerful transformations that allow for rapid formation of 1,2-disubsituted arenes.
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As of 2003, there were 126 GAs identified from plants, fungi, and bacteria. Gibberellins are tetracyclic diterpene acids. There are two classes based on the presence of either 19 or 20 carbons. The 19-carbon gibberellins, such as gibberellic acid, have lost carbon 20 and, in place, possess a five- member lactone bridge that links carbons 4 and 10.
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Cholesterol is a tetracyclic alcohol and a type of sterol. Added to the sterol frame with the alcohol group at position 3 are 2 methyl groups at carbon positions 10 and 13 and a 2-isooctyl group at position 17. The molecule is unsaturated at position 5,6 with an alkene group. The total number of stereocenters is 8.
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The structure of the tetracyclic ring of cholesterol contributes to the fluidity of the cell membrane, as the molecule is in a trans conformation making all but the side chain of cholesterol rigid and planar. In this structural role, cholesterol also reduces the permeability of the plasma membrane to neutral solutes, hydrogen ions, and sodium ions.
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The Bergman-Venemalm synthesis was first reported in 1988. It focuses on building the tetracyclic unit before introducing the second indole unit. Requiring five reactions starting from indole, all of which are reasonably high yielding, this is an effective method for synthesizing yeuhchukene. Importantly, only one diastereomer is produced, with stereoselectivity being introduced in the 3rd reaction.
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The F-ring sugar is the N,N-dimethyl derivative of vancosamine, which is the sugar found in the glycopeptide antibiotic vancomycin. These compounds exhibit in vitro antitumor activity by DNA alkylation, where the two proximal amino sugars, D-angolosamine and N,N-dimethyl-L-vancosamine, play a key role in sequence recognition in intercalation of the tetracyclic chromophore.
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Protopanaxadiol (PPD) is an organic compound characterizing a group of ginsenosides. It is a dammarane-type tetracyclic terpene sapogenin found in ginseng (Panax ginseng) and in notoginseng (Panax pseudoginseng). Just what protopanaxadiol's metabolites do inside the human body is still unclear. One study suggests it has rapid, non-genomic effects on endothelial cells, binding to the glucocorticoid and oestrogen beta receptors.
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The biosynthesis of hibarimicinone was initially hypothesized to be produced from a polyketide synthase. Through 13C-labelling and blocked mutants of the TP-A0121 strain, Oki et al. demonstrated that hibarimicinone is produced by an oxidative coupling of two tetracyclic polyketides, which undergo an oxidative cyclization to generate the ether ring. The hibarimicinone monomer is formed initially by a Type II polyketide synthase.
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Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant which is used primarily in the treatment of depression in Europe and elsewhere in the world. It is a tetracyclic antidepressant (TeCA). Mianserin is closely related to mirtazapine, both chemically and in terms of its actions and effects, although there are significant differences between the two drugs.
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This picture illustrates the main steps in the Kreis synthesis of (-)Dendrobine There have been 3 successful enantioselective syntheses of dendrobine reported with yields ranging from 0.2-4.0%. The structure of dendrobine is intriguing due to its tetracyclic ring system with seven contiguous stereocenters. Most recently, a full synthesis of (-)-dendrobine was carried out by Kreis et al. with a yield of 4.0%.
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Aphidicolin is a tetracyclic diterpene antibiotic isolated from the fungus, Cephalosporum aphidicola with antiviral and antimitotic properties. Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication. It blocks the cell cycle at early S phase. It is a specific inhibitor of DNA polymerase Alpha and Delta in eukaryotic cells and in some viruses (vaccinia and herpesviruses) and an apoptosis inducer in HeLa cells.
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S. usambarensis root bark also holds the less active afrocurarine, the monomeric tetracyclic alkaloid akagerine, the non-terpenoid alkaloids harmane and melinonine F and the monoquaternary alkaloids malindine and Isomalindine, which belong to the group of trinitrogenated alkaloids. Four root alkaloids, the dimeric usambarensines, are of the corynanthine class. Several of the alkaloids in S. usambarensis have promising anticancer or antimalarial properties, justifying further research.
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Certain other substances can cause adverse effects that may be severe. Combination of levothyroxine with ketamine may cause hypertension and tachycardia; and tricyclic and tetracyclic antidepressants increase its toxicity. Lithium, though, can cause hyperthyroidism (but most often hypothyroidism) by affecting iodine metabolism of the thyroid itself, thus inhibiting synthetic levothyroxine, as well. Soy, walnuts, fiber, calcium supplements, and iron supplements can also adversely affect absorption.
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Cunninghamella elegans is a microbial model of mammalian drug metabolism. The use of this fungus could reduce the over-all need for laboratory animals. C. elegans is able to transform the tricyclic antidepressants amitriptyline and doxepin, the tetracyclic antidepressant mirtazapine, the muscle relaxant cyclobenzaprine, the typical antipsychotic chlorpromazine as well as the antihistamine and anticholinergic methdilazine and azatadine. It is also able to transform the antihistamines brompheniramine, chlorpheniramine and pheniramine.
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Chemical structure of solanidine, a steroidal alkaloid found in potatoes Steroidal alkaloids have organic ring backbones which feature nitrogen-based functional groups. More specifically, they are distinguished by their tetracyclic cyclopentanophenanthrene backbone that marks their close relationship with sterols. They fall in two major categories: Solanum alkaloids and Veratrum alkaloids. A Steroidal alkaloid has also been found in Chonemorpha fragrans (Frangipani vine), 'chonemorphine' was used to treat intestinal infections in Wistar rats.
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The Wieland–Miescher ketone is the Robinson annulation product of 2-methyl-cyclohexane-1,3-dione and methyl vinyl ketone. This compound is used in the syntheses of many steroids possessing important biological properties and can be made enantiopure using proline catalysis. Wieland–Miescher ketone F. Dean Toste and co-workers have used Robinson annulation in the total synthesis of (+)-fawcettimine, a tetracyclic Lycopodium alkaloid that has potential application to inhibiting the acetylcholine esterase.
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The synthesis of gambierol consists of two tetracyclic precursor molecules, one alcohol and one acetic acid, that fuse together. The whole synthesis of gambierol is depicted in the figure below. After obtaining the octacyclic backbone, the tail is added via Stille coupling. The acetic acid (compound 1) and alcohol (compound 2) are converted to compound 3. The reaction of compound 3 with the titanium alkylidene from dibromide 1,1-dibromoethane, provides cyclic enol ether (compound 4).
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The silicon double bond in the resulting compound has a bond length of 227 picometer (second largest ever found) with trans-bent angles 33° and 31° (by X-ray diffraction). :Tricyclic Disilenes with Highly Strained Si-Si Double Bonds In addition to this the substituents around the Si-Si bond are twisted by 43°. The disilene isomerizes to a tetracyclic compound by heating at 110°C in xylene thereby releasing its strain energy.
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Like other members of the family Cucurbitaceae, gourds contain cucurbitacins that are known to be cytotoxic at a high concentration. The tetracyclic triterpenoid cucurbitacins present in fruits and vegetables of the cucumber family are responsible for the bitter taste, and could cause stomach ulcers. In extreme cases, people have died from drinking the juice of gourds. The toxic cases are usually due to the gourd being used to make juice, which the drinkers described as being unusually bitter.
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Activity was found to be abolished by nitrogen substitution, 2, 5 and 5'-position substitution, hydroxylation of the benzene ring, hydroxylation of C9-C10 double bond and deletion of 7,7-dimethyl group. The activity was unaffected by saturation of the C9-C10 double bond. It was concluded that biological activity is dependent upon an optimal conformation defined by a narrowly fixed angle between the planes of the C6-indole and the tetracyclic unit. Yuehchukene also possesses estrogenic activity.
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Its reversibility enables it to quickly activate and inhibit itself, making the molecule a specific inhibitor both in vitro and in cellulo. Pyr1 can be described as a tetracyclic molecule with a simple structure. Its few radicals are widely expanded along the benzene rings, distinguishing a benzoyloxy group in the ninth carbon and two methyl radicals in carbon five and eleven. There is also a ketone group in carbon one and two hydrogen radicals in carbons two and six.
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Pluramycin A is an antibiotic/anticancer compound that inhibits nucleic acid biosynthesis. The pluramycin family of natural products are an important group of complex C-aryl glycoside antibiotics that possess the tetracyclic 4H-anthra[1,2-b]pyran-4,7,12-trione moiety A–D as an aromatic core. The D-ring is adorned with two deoxyaminosugars that are appended by C-aryl glycosidic linkages. The E-ring sugar is angolosamine, a carbohydrate that is also found in the antibiotic angolamycin.
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Ciclazindol (WY-23409) is an antidepressant and anorectic drug of the tetracyclic chemical class that was developed in the mid to late 1970s, but was never marketed. It acts as a norepinephrine reuptake inhibitor, and to a lesser extent as a dopamine reuptake inhibitor. Ciclazindol has no effects on the SERT, 5-HT receptors, mACh receptors, or α-adrenergic receptors, and has only weak affinity for the H1 receptor. As suggested by its local anesthetic properties, ciclazindol may also inhibit sodium channels.
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The Micalizio route (2011) achieved the end product in 9 steps from a commercially available acetyl-pyridine. Notable reactions include a [2,3]-Still-Wittig rearrangement and a conformationally-controlled intramolecular Mannich cyclization. The Weinreb group (2014) used a conjugative addition of an indole precursor to an oxime-substituted nitrosoalkene to generate the tetracyclic skeleton of conolidine in 4 steps. Takayama and colleagues (2016) synthesized conolidine and apparicine through a gold(I)-catalyzed exo-dig synthesis of a racemic piperidinyl aldehyde.
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Cucurbitacin E is a biochemical compound from the family of cucurbitacins. These are found in plants which are member of the family Cucurbitaceae, most of them coming from traditional Chinese medicinal plants, but also in other plants such as pumpkins and gourds. Cucurbitacin E is a highly oxidated steroid consisting of a tetracyclic triterpene. Specific changes on this molecule under certain conditions can generate other types of cucurbitacins such as cucurbitacin I, J, K and L. It is being investigated for its potential biological effects.
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Platensimycin structure Scientists at Merck have recently discovered a novel antibiotic lead compound with potential medicinal applications called platensimycin as seen in the adjacent picture. Initial synthesis gave a racemic form of the compound using an intramolecular etherification reaction of the alcohol motifs and the double bond. Yamamoto reports the use of an alternative intramolecular Robinson annulation to provide a straightforward enantioselective synthesis of tetracyclic core of platensimycin. The key Robinson annulation step was reported to be accomplished in one pot using L-proline for chiral control.
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S. spinosa was isolated from soil collected inside a nonoperational sugar mill rum still in the Virgin Islands. Spinosad is a mixture of chemical compounds in the spinosyn family that has a generalized structure consisting of a unique tetracyclic ring system attached to an amino sugar (D-forosamine) and a neutral sugar (tri-Ο-methyl-L-rhamnose). Spinosad is relatively nonpolar and not easily dissolved in water. Spinosad is a novel mode-of-action insecticide derived from a family of natural products obtained by fermentation of S. spinosa.
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In contrast to Type I PKS systems, the synthetic enzymes (KS, CLF, ACP and AT) are not attached covalently to each other, and may not even remain associated during each step of the polyketide chain synthesis. After the 21-carbon decaketide chain of DXR is completed, successive modifications are made to eventually produce a tetracyclic anthracycline aglycone (without glycoside attached). The daunosamine amino sugar, activated by addition of Thiamine diphosphateTDP, is created in another series of reactions. It is joined to the anthracycline aglycone and further modifications are done to produce first daunorubicin then DXR.
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All triterpenoids are synthesized via the cyclization of the C30 isoprenoid chain, squalene. Eukaryotes use oxidosqualene cyclase and several other enzymes to create the tetracyclic skeleton found in steroids, a process that requires molecular oxygen. Bacteria use a similar enzyme (shc) to create the pentacyclic hopanoid precursor, diploptene; however, this biosynthesis does not require oxygen. It was recently discovered that tetrahymanol-producing bacteria form diploptene using shc then elongate the final cyclopentane into a fifth The molecular structures of cholesterol (A), tetrahymanol (B), and diploptene (C)ring using tetrahymanol synthase (ths).
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Aptazapine (developmental code name CGS-7525A) is a tetracyclic antidepressant (TeCA) which was assayed in clinical trials for the treatment of depression in the 1980s but was never marketed. It is a potent α2-adrenergic receptor antagonist with ~10x the strength of the related compound mianserin and has also been shown to act as a 5-HT2 receptor antagonist and H1 receptor inverse agonist, while having no significant effects on the reuptake of serotonin or norepinephrine. Based on its pharmacological profile, aptazapine may be classified as a noradrenergic and specific serotonergic antidepressant (NaSSA).
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A number of Duroia species, and possibly all, are capable of biochemical interactions inhibiting the growth of neighbouring plants. Analysis of root extracts from Duroia hirsuta have yielded a strong plant growth inhibitor plumericin, a tetracyclic iridoid lactone. This process, common amongst plants, is termed allelopathy. In the case of Duroia hirsuta, the chemical inhibitor is aided by the leafcutter ant Myrmelachista schumanni resident on and in the tree, and playing an active role in suppressing and destroying plant growth in the vicinity of their host by injecting and spraying formic acid.
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423 They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds. Although TCAs are sometimes prescribed for depressive disorders, they have been largely replaced in clinical use in most parts of the world by newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). Adverse effects have been found to be of a similar level between TCAs and SSRIs.
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Digitoxigenin, the cardenolide substructure of cerberin, with the tetracyclic array of all-carbon steroid rings at its core, to which is attached the butenolide-type, oxygen-containing lactone substituent. Cerberin, like all cardiac glycosides, has as its core a steroid-type set of four carbocycles (all-carbon rings). In cerberin, this steroid core is connected, first, to a separate oxygen-containing lactone ring (shown here, upper right of box), and second, to a sugar substituent (shown in infobox structure, left of image). There are two types of cardiac glycosides depending on the characteristics of the lactone moiety.
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Duroia hirsuta is a myrmecophyte tree species from the Amazon Forest. It is one of some 37 species of Duroia, which are shrubs or canopy trees in the family Rubiaceae, favouring ants (myrmecophilous), and occurring in Central America as far north as Mexico, the Amazon Basin, the Guiana Shield, the Brazilian Atlantic coast and planalto. A number of Duroia species, and possibly all, are capable of biochemical interactions inhibiting the growth of neighbouring plants. Analysis of root extracts from Duroia hirsuta have yielded a strong plant growth inhibitor plumericin, a tetracyclic iridoid lactone, and duroin, another iridoid lactone.
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The molecule they identified, platensimycin (C24H27NO7, relative molecular mass 441.47), comprises two distinct structural elements connected by an amide bond. The Merck group showed that platensimycin has potent, broad-spectrum Gram-positive activity in vitro and exhibits no cross-resistance to other key antibiotic-resistant bacteria including Methicillin-resistant Staphylococcus aureus(MRSA), vancomycin-intermediate S. aureus, vancomycin-resistant Enterococci, and linezolid-resistant and macrolide-resistant pathogens. As confirmed by total synthesis of racemic platensimycin, its structure consists of a 3-amino-2,4-dihydroxybenzoic acid polar part linked through an amide bond to a lipophilic tetracyclic ketolide.
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Possible substitutions of the Mazindol molecular structure. See: List of Mazindol analogues Mazindol is usually considered a non-habituating (in humans, and some other mammals, but is habituating for e.g. Beagles) tetracyclic dopamine reuptake inhibitor (of somewhat spurious classification in the former). It is a loosely functional analog used in cocaine research; due in large part to N-Ethylmaleimide being able to inhibit approximately 95% of the specific binding of [3H]Mazindol to the residues of the MAT binding site(s), however said effect of 10 mM N-Ethylmaleimide was prevented in its entirety by just 10 μM cocaine.
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Yohimbine, historically used as an aphrodisiac, is sometimes used in veterinary medicine (although now largely replaced by atipamezole) for reversing the effects of α2s such as medetomidine that are used as sedatives during surgery. The tetracyclic antidepressants mianserin and mirtazapine are α2 blockers, although their efficacy as antidepressants may come from their activity at other receptor sites. Mechanistically, α2 blockers increase adrenergic, dopaminergic and serotonergic neurotransmitters and induce insulin secretion, decreasing blood sugar levels. Withdrawal from α2 blockers can be difficult or dangerous as the global downregulation of neurotransmitters may cause symptoms of depression and other neurological problems, and increased blood sugar levels together with decreased insulin sensitivity can cause diabetes.
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In acidic solution, the sulfenic acid is isolated before reaction with one or more cysteines accessible from the luminar surface of the enzyme, a tetracyclic sulfenamide. This is a planar molecule thus any enantiomer of a PPI loses stereospecifity upon activation. The effectiveness of these drugs derives from two factors: their target, the H+/K+ ATPase which is responsible for the last step in acid secretion; therefore, their action on acid secretion is independent of the stimulus to acid secretion, of histamine, acetylcholine, or other yet to be discovered stimulants. In addition, their mechanism of action involves covalent binding of the activated drug to the enzyme, resulting in a duration of action that exceeds their plasma half-life.
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Many of the key psychoactive compounds in M. speciosa are indole alkaloids related to mitragynine, which is a tetracyclic relative of the pentacyclic indole alkaloids, yohimbine and voacangine. In particular, mitragynine and 7-hydroxymitragynine (7-HMG) compose significant proportions of the natural products isolable from M. speciosa; e.g., in one study, mitragynine was 12% by weight from Malaysian leaf sources, versus 66% from Thai sources, and 7-hydroxymitragynine constituted ~2% by weight. In addition, at least 40 other compounds have been isolated from M. speciosa leaves, including ~25 additional alkaloids, including raubasine/ajmalicine (originally isolated from Rauvolfia serpentina), corynantheidine (also found in Pausinystalia johimbe), as well as mitraphylline, mitragynine pseudoindoxyl, and rhynchophylline.
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The site has a long history of research in the area of neuromuscular blockers, which are commonly used during surgery, and was responsible for the identification of rocuronium as well as a number of other drugs. In another major advance the reversal agent sugammadex was the first selective relaxant binding agent (SRBA) for Neuromuscular Block Reversal to be identified, and has recently entered the market in Europe. On the psychiatric front researchers at Newhouse supported the development of mirtazepine, a novel tetracyclic anti-depressant which has become widely prescribed throughout the world. More recently the site was closely involved in supporting the introduction of the anti-psychotic asenapine which has just been launched for the treatment of schizophrenia and bipolar disorder.
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Antidepressants are considered a first line treatment for depression. While these medications are assessable to most, and effective enough to reduce clinical manifestations and increase quality of life for many suffering from depression, they are often not effective for severe depression and they come with a large array of side effects. There are multiple types of antidepressant medications: selective serotonin reuptake inhibitors (SSRIs), noradrenaline uptake inhibitors (NRIs), monoamine oxidase inhibitors (MAOIs), as well as tricyclic and tetracyclic antidepressants, all of which have a different list of unpleasant side effects. Side effects of MAOIs include tremors, insomnia, increased appetite leading to weight gain, blurred vision, urinary retention, headaches, acute hypertension and can even lead to intracranial hemorrhage when taken with food substances containing tyramine.
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Trimipramine is a very potent antihistamine; it has the third highest affinity for the H1 receptor (Ki = 0.27 nM) after mirtazapine (Ki = 0.14 nM) and doxepin (Ki = 0.24 nM) among the TCAs and tetracyclic antidepressants (TeCAs). The TeCA mianserin (Ki = 0.40) and the TCA amitriptyline (Ki = 1.0) are also very potent H1 receptor antagonists, whereas other TCAs and TeCAs are less potent. These TCAs and TeCAs, including trimipramine, are far more potent than the standard antihistamine diphenhydramine (approximately 800 times for doxepin and 250 times for trimipramine), and are among the most potent antihistamines available. Trimipramine is also an antagonist of the H2 receptor with lower potency and has been found to be effective in the treatment of duodenal ulcers.
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As a MAO inhibitor, safinamide can theoretically cause hypertensive crises, serotonin syndrome and other severe side effects when combined with other MAO inhibitors or with drugs that are known to interact with MAO inhibitors, such as pethidine, dextromethorphan, selective serotonin reuptake inhibitors (SSRIs), serotonin–noradrenaline reuptake inhibitors (SNRIs), tricyclic and tetracyclic antidepressants. An interaction with tyramine, a substance found in various foods, could be expected by the same reasoning but has been excluded in studies. Safinamide should not be given with opioids; some fatal reactions have occurred. Another theoretical interaction is with drugs with affinity to the transporter protein ABCG2 (also known as BCRP), such as pitavastatin, pravastatin, ciprofloxacin, methotrexate, and diclofenac; a study with the latter has shown no clinical relevance.
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The irregularities in symmetry can be due to the androecium, to the perianth, or both at the same time. In the great majority of species, the flowers have a differentiated perianth with a calyx and corolla (with five sepals and five petals, respectively) an androecium with five stamens and two carpels forming a gynoecium with a superior ovary (they are therefore referred to as pentamers and tetracyclic). The stamens are epipetalous and are typically present in multiples of four or five, most commonly four or eight. They usually have a hypogynous disk. The calyx is gamosepalous (as the sepals are joined together forming a tube), with the (4)5(6) segments equal, it has five lobes, with the lobes shorter than the tube, it is persistent and often accrescent.
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An orexigenic, or appetite stimulant, is a drug, hormone, or compound that increases appetite and may induce hyperphagia. This can be a medication or a naturally occurring neuropeptide hormone, such as ghrelin, orexin or neuropeptide Y, which increases hunger and therefore enhances food consumption. Usually appetite enhancement is considered an undesirable side effect of certain drugs as it leads to unwanted weight gain, but sometimes it can be beneficial and a drug may be prescribed solely for this purpose, especially when the patient is suffering from severe appetite loss or muscle wasting due to cystic fibrosis, anorexia, old age, cancer or AIDS. There are several widely used drugs which can cause a boost in appetite, including tricyclic antidepressants (TCAs), tetracyclic antidepressants, natural or synthetic cannabinoids, first-generation antihistamines, most antipsychotics and many steroid hormones.
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Biosynthesis of berberine The alkaloid berberine has a tetracyclic skeleton derived from a benzyltetrahydroisoquinoline system with the incorporation of an extra carbon atom as a bridge. Formation of the berberine bridge is rationalized as an oxidative process in which the N-methyl group, supplied by S-adenosyl methionine (SAM) is oxidized to an iminium ion, and a cyclization to the aromatic ring occurs by virtue of the phenolic group. Reticuline is known as the immediate precursor of protoberberine alkaloids in plants. Berberine is an alkaloid derived from tyrosine. L-DOPA and 4-hydroxypyruvic acid both come from L-tyrosine. Although two tyrosine molecules are used in the biosynthetic pathway, only the phenethylamine fragment of the tetrahydroisoquinoline ring system is formed via DOPA, the remaining carbon atoms come from tyrosine via 4-hydroxyphenylacetaldehyde.
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Hibarimicinone is an organic atropisomeric small molecule, derived from hibarimicins, which are isolated from the microbial culture strain of Microbispora rosea from the Hibari region of Japan.Hori, H.; Higashi, K.; Ishiyama, T.; Uramoto, M.; Uehara, Y.; Oki, T. Tetrahedron Lett. 1996 37, 2785-2788Kajiura, T.; Furumai, T.; Igarashi, Y.; Hori, H.; Higashi, K.; Ishiyama, T.; Uramoto, M.; Uehara, Y.; Oki, T. J. Antibiot. 1998, 51, 394-401Hori, H.; Kajiura, T.; Igarashi, Y.; Hori, H.; Higashi, K; Ishiyama, T.; Uramoto, M; Uehara, Y.; Oki, T. J. Antibiot. 2002, 55, 53-60Hori, H.; Kajiura, T.; Igarashi, Y.; Furumai, T; Higashi, K.; Ishiyama, T; Uramoto, M; Uehara, Y; Oki, T. J. Antibiot., 2002, 55, 46-52 Analysis of the bacteria identified a new class of molecule containing a dimeric-tetracyclic polyketide backbone, which are now known as the hibarimicins.
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Longifolene, a terpene natural product, and an example of a tricyclic molecule Cholesterol, another terpene natural product, in particular, a steroid, a class of tetracyclic molecules Benzo[a]pyrene, a pentacyclic compound both natural and man-made Pagodane, a man-made polycyclic compound In the field of organic chemistry, a polycyclic compound is an organic compound featuring several closed rings of atoms, primarily carbon. These ring substructures include cycloalkanes, aromatics, and other ring types. They come in sizes of three atoms and upward, and in combinations of linkages that include tethering (such as in biaryls), fusing (edge-to-edge, such as in anthracene and steroids), links via a single atom (such as in spiro compounds), bridged compounds, and longifolene. Though poly- literally means "many", there is some latitude in determining how many rings are required to be considered polycyclic; many smaller rings are described by specific prefixes (e.g.
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A series of 7 further steps—condensation to form trans-butenoate 22, thermal intramolecular Diels-Alder reaction to create the tetracyclic endiantric core structure 23, desilylation to unmask alcohol 24, bromination and nitrile formation (as described above) to give 25 and 26, respectively, then hydrolysis of the methyl ester and repeat of the earlier DIBAL/acid hydrolysis sequence—generated the endiantric core structure with pendant aldehyde, 28, that was poised for the final step. Its treatment with diethyl cinnamylphosphonate and LDA at low temperature in THF (generating en route the anionic olefination reagent) formed the desired diene in good yield in a "geometrically controlled manner", thus providing the desired endiandric acid C product. Initial electrocyclizations in Nicolaou endiandric acid C synthesis, to provide diol 17 shown in the main scheme. This key intermediate is then ready for elaboration into the olefin which can undergo the further 6π[4+2] (Diels-Alder) cycloaddition reaction shown in the main scheme, to provide the title natural product.
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It was originally used to describe the complex mixture of petroleum-based acids when the analytical methods available in the early 1900s could identify only a few naphthene-type components with accuracy. Today "naphthenic" acid is used in a more generic sense to refer to all of the carboxylic acids present in petroleum, whether cyclic, acyclic, or aromatic compounds, and carboxylic acids containing heteroatoms such as N and S. Although commercial naphthenic acids often contain a majority of cycloaliphatic acids, multiple studies have shown they also contain straight chain and branched aliphatic acids and aromatic acids; some naphthenic acids contain >50% combined aliphatic and aromatic acids. Naphthenic acids are represented by a general formula CnH2n-z O2, where n indicates the carbon number and z specifies a homologous series. The z is equal to 0 for saturated, acyclic acids and increases to 2 in monocyclic naphthenic acids, to 4 in bicyclic naphthenic acids, to 6 in tricyclic acids, and to 8 in tetracyclic acids.
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Biomimetic synthesis is an area of organic chemical synthesis that is specifically biologically inspired. The term encompasses both the testing of a "biogenetic hypothesis" (conjectured course of a biosynthesis in nature) through execution of a series of reactions designed to parallel the proposed biosynthesis, as well as programs of study where a synthetic reaction or reactions aimed at a desired synthetic goal are designed to mimic a one or more known enzymic transformations of an established biosynthetic pathway. The earliest generally cited example of a biomimetic synthesis is Sir Robert Robinson's organic synthesis of the alkaloid tropinone. 500px A more recent example is E.J. Corey's carbenium-mediated cyclization of an engineered linear polyene to provide a tetracyclic steroid ring system, which built upon studies of cationic cyclizations of linear polyenes by the Albert Eschenmoser and Gilbert Stork, and the extensive studies of the W.S. Johnson to define the requirements to initiate and terminate the cyclization, and to stabilize the cationic carbenium group during the cyclization (as nature accomplishes via enzymes during biosynthesis of steroids such as cholesterol).
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Starting point for the Woodward synthesis was the hydroquinone 1 that was converted to cis-bicycle 2 in a Diels-Alder reaction with butadiene. Conversion to the desired trans isomer 5 was accomplished by synthesis of the sodium enolate salt 4 (benzene, sodium hydride) followed by acidification. Reduction (lithium aluminum hydride) then gave diol 6, a dehydration (HCl/water) gave ketol 7, deoxygenation of its acetate by elemental zinc gave enone 8, formylation (ethyl formate) gave enol 9, Michael ethyl vinyl ketone addition (potassium t-butoxide/t-butanol) gave dione 11 which on reaction with KOH in dioxane gave tricycle 12 in an aldol condensation with elimination of the formyl group. In the next series of steps oxidation (osmium tetroxide) gave diol 13, protection (acetone/copper sulfate) gave acetonide 14, hydrogenation (palladium-strontium carbonate) gave 15, formylation (ethyl formate) gave enol 16 which protected as the enamine 17 (N-methylaniline/methanol) gave via the potassium anion 18, carboxylic acid 19 by reaction with cyanoethylene using triton B as the base. Cholesterol synthesis Woodward 1 Acid 19 was converted to lactone 20 (acetic anhydride, sodium acetate) and reaction with methylmagnesium chloride gave tetracyclic ketone 21. Treatment with periodic acid (dioxane) and piperidine acetate (benzene) gave aldehyde 24 through diol 22 (oxidation) and dialdehyde 23 (aldol condensation).
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