Tetracyclic Research Articles

4+2] Cycloadditions of 1,2,4,5-Tetrazines and Cyclopropenes − Synthesis of 3,4-Diazanorcaradienes and Tetracyclic Aliphatic Azo Compounds

1,2,4,5-Tetrazines 1 readily react with cyclopropenes 2 to form 3,4-diazanorcaradienes 3, 4, 7 and 8 in a cycloaddition − cycloelimination sequence. Compounds 3 and 4 still act as 1,3-dienes with cyclopropenes 2, producing aliphatic azo compounds 5 and 6, versatile starting compounds in thermolysis and photolysis reactions.

Lewis acid-catalyzed successive skeletal rearrangement of cyclobutene-fused diphenylhomoquinone

The tricyclic enedione, which was synthesized in the [2+2] photocycloaddition of homoquinone with alkyne, underwent a novel Lewis acid-mediated skeletal rearrangement to provide bi-, tri- and tetracyclic cage compounds, depending on the identity of the Lewis acid used. The prolonged reaction and the independent treatment of the intermediary products by other Lewis acids revealed that the reaction proceeds through successive, multi-step transformations involving a cyclobutene ring-cleavage, an intramolecular Friedel–Crafts addition, and a cyclopropane ring-opening as well as an intramolecular cyclization. The product distributions were governed by the identity of the Lewis acid and the coordinated carbonyl site.

The Cycloaddition-Cycloelimination Pathway to Homotropilidenes − Synthesis and Properties of Homotropilidenes

The cycloaddition-cycloelimination reaction sequence between 3,6-disubstituted 1,2,4,5-tetrazines 9 and various cyclopropenes 10 provides 3,4-diazanorcaradienes 11, which undergo [4+2] cycloadditions with additional cyclopropenes 10 to form tetracyclic azo compounds 12. Photolysis of these compounds, with accompanying loss of nitrogen, affords homotropilidenes (bicyclo[5.1.0]octa-2,5-dienes) 13−26. Substituents at various positions of the homotropilidene skeleton have been observed to exert significant influences on the Cope rearrangement rate and, in cases of unsymmetrically substituted homotropilidenes, on the equilibrium positions.

4+2] Cycloadditions of 1,2,4,5-Tetrazines and Cyclopropenes − Synthesis of 3,4-Diazanorcaradienes and Tetracyclic Aliphatic Azo Compounds

1,2,4,5-Tetrazines 1 readily react with cyclopropenes 2 to form 3,4-diazanorcaradienes 3, 4, 7 and 8 in a cycloaddition − cycloelimination sequence. Compounds 3 and 4 still act as 1,3-dienes with cyclopropenes 2, producing aliphatic azo compounds 5 and 6, versatile starting compounds in thermolysis and photolysis reactions.

Addition Reactions of Maleic Anhydride to a Disilene and a Tetrasilabuta-1,3-diene: Formation of Bi- and Tetracyclic Compounds1,2

The reaction of hexakis(2,4,6-triisopropylphenyl)tetrasilabutadiene with maleic anhydride (3) furnishes the 2,9-dioxa-5,6,7,8-tetrasilatetracyclodecan-3-one derivative 4, presumably by a sequence of two consecutive [2 + 2] cycloadditions. Tetrakis(2,4,6-triisopropylphenyl)disilene reacts with 3 to afford the bicyclic 1,2-dihydrofuro[3,2-d][1,2,3]oxadisilol-5(6H)-one derivative 5 via a formal [2 + 3] cycloaddition and a 1,2-hydrogen shift. The structures of 4 and 5 were determined by X-ray crystallography.

Difurocoumarins: Psoralen analogs as photochemotherapeutic agents

AbstractNew tetracyclic psoralen‐like compounds have been synthesized, which are characterized by two furan rings angularly condensed on the coumarin nucleus and are therefore called difurocoumarins. This structural feature may favour the intercalation into the DNA helix and then monofunctionally photoreaction with DNA bases. Their synthesis started from 5,7‐dihydroxy‐4‐methylcoumarin, which was condensed with α‐halo‐ketones; the resulting ketoethers were then cyclized to give the title compounds.

Formal total synthesis of (+/-)-gamma-lycorane and (+/-)-1-deoxylycorine using the [4+2]-cycloaddition/rearrangement cascade of furanyl carbamates.

The total syntheses of gamma-lycorane and (+/-)-1-deoxylycorine were accomplished using an intramolecular Diels-Alder cycloaddition of a furanyl carbamate as the key step. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The key intermediate used in both syntheses corresponds to hexahydroindolinone 20. Removal of the t-Boc group in 20 followed by reaction with 6-iodobenzo[1,3]dioxole-5-carbonyl chloride afforded enamide 22. Treatment of this compound with Pd(OAc)(2) employing the Jeffrey modification of the Heck reaction provided the galanthan tetracycle 24 in good yield. Compound 24 was subsequently converted into (+/-)-gamma-lycorane using a four-step procedure to establish the cis-B,C-ring junction. A radical-based cyclization of the related enamide 33 was used for the synthesis of 1-deoxylycorine. Heating a benzene solution of 33 with AIBN and n-Bu(3)SnH at reflux gave the tetracyclic compound 38 possessing the requisite trans fusion between rings B and C in good yield. After hydrolysis and oxidation of 38 to 40, an oxidative decarboxylation reaction was used to provide the C(2)(-)C(3)(-)C(12) allylic alcohol unit characteristic of the lycorine alkaloids. The resulting enone was eventually transformed into (+/-)-1-deoxylycorine via known synthetic intermediates.

Synthesis of a new tetracyclic condensed system: 7,8-dihydro-6h-furo[2', 3' :1,2]cyclohepta-[c]isoquinolin-8-one

Synthesis of a new tetracyclic condensed system: 7,8-dihydro-6h-furo[2', 3' :1,2]cyclohepta-[c]isoquinolin-8-one

ChemInform Abstract: Pyridazines. Part 91. Synthesis of Substituted Tri- and Tetracyclic Compounds Bearing a Pyridazine Core and Their Biological Evaluation as Antimycobacterial Agents.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Molecular Complexity from Aromatics: Synthesis and Photoreaction of endo-Tricyclo[5.2.2.02,6]undecanes. Formal Total Syntheses of (±)-Coriolin

Formal syntheses of coriolin 1, a triquinane metabolite isolated from Coriolus consors, are described. Oxidation of 6-methyl saligenin 2 in the presence of cyclopentadiene gave the tricyclic keto epoxide 4 which was elaborated to tricyclo[5.2.2.02,6]undecenones 5 and 18 containing the major structural and stereochemical features of coriolin, in latent form. Triplet sensitized 1,2-acyl shifts in 5 and 18 gave tetracyclic compounds 6 and 19 in a stereoselective manner. Reductive cleavage of cyclopropane rings in 6 and 19 with H2/Pd-C and TBTH-AIBN respectively, furnished the functionalised triquinanes 7 and 20b which are known precursors for coriolin.

The fate of the tryptophan stereocenter in the synthesis of 7,10,16,16a-tetrahydro-11 H-quinazolino[2′,3′:3,4]pyrazino[1,2- b]β-carboline-5,8-diones

Condensation reactions of anthranilic acid with iminoethers 14– 17 derived from tetracycles 9– 13 to give the title hexacyclic compounds reflect a preferred trans-relationship for H(10)–H(16a) protons in C(7)-unsubstituted products and a cis-relatioship for H(7)–H(16a) protons in C(10)-unsubstituted analogs. This synthetic strategy is limited by the steric hindrance of the substituent at C(10). Theoretical calculations are in agreement with the experimental results. The regioselectivity in favor of the linear tetracyclic compound 11 with respect to 12 has also been confirmed.

Pyridazines 91. Synthesis of substituted tri- and tetracyclic compounds bearing a pyridazine core and their biological evaluation as antimycobacterial agents.

Starting from substituted 3,6-dichloropyridazine-4-carboxamides (2, 3) tri- and tetracyclic compounds (4, 5) could be smoothly prepared. Structural modifications of interest with regard to biological activity were performed by N-alkylation and reductive dehalogenation. The new substituted heterocyclic compounds were screened as antimycobacterial agents; the influence of the substitution pattern on activity is discussed.

Electrocyclic ring-opening/pi-allyl cation cyclization reaction sequences involving gem-dihalocyclopropanes as substrates: application to syntheses of (+/-)-, (+)-, and (-)-gamma-lycorane.

The readily prepared gem-dibromocyclopropanes (+/-)-13 and (+/-)-19 each engage in a silver(I)-promoted electrocyclic ring-opening/pi-allyl cation cyclization sequence to deliver the hexahydroindole (+/-)-20, which participates in a Suzuki cross-coupling reaction with arylboronic acid 3 to give the tetracyclic compound (+/-)-21. Catalytic hydrogenation of this last compound proceeds in a completely stereoselective manner to give the saturated analogue (+/-)-24, which undergoes Bischler-Napieralski cyclization on reaction with phosphorus oxychloride. The resulting lactam (+/-)-25 is then reduced with lithium aluminum hydride to give (+/-)-gamma-lycorane [(+/-)-1]. By using (-)-menthyl-derived carbamates 27 and 28, this chemistry has been extended to the synthesis of the (+)- and (-)-modifications of the title compound.

ChemInform Abstract: The Strategy for Co2(CO)8‐Catalyzed Double Carbonylative [2 + 2 + 1] Cycloaddition or [2 + 2 + 2] Cycloaddition Reaction of Triynes: A New Synthesis Method for Tetracyclic Compounds.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Structural chemistry of polycyclic heteroaromatic compounds. Part XI. Photoelectron spectra and electronic structures of tetracyclic hetarenes of the triphenylene type

The UV photoelectron spectra of several tetracyclic heteroaromatic compounds ( 2– 9) which are π-isoelectronic with triphenylene ( 1) have been recorded and analysed making use of semiempirical AM1 and PM3 as well as ab initio/DFT B3LYP calculations. In one series of compounds ( 2– 7), the peripheral benzene rings of 1 are successively substituted by thiophene rings that are either [b]- or [c]-annellated with the central benzene unit. In 2– 7 only marginal shifts are found for most of the IPs of electrons. In the benzotrithiophenes 5– 7, a systematic variation is displayed by IP( π 7). Compared to 1, the π electron system of benzo[c]trithiophene ( 7) is approximately two times as much destabilized as in the isomers 5 and 6 with [b]annellated thiophene rings. The IP[ n(S)] values of the thiophene derivatives 2– 7 indicate that these orbitals are clearly destabilized relative to thiophene. The same holds for the n(O) orbital of the furane derivative 9 in comparison with that of furane. In 9, only the higher π MOs ( π 7– π 9) are destabilized whereas the lower levels ( π 1– π 4) are stabilized, and those in between ( π 5– π 6) remain essentially unshifted. In the pyrrole derivative 8, all π MOs are substantially destabilized by about 0.5–1.6 eV relative to 1.

Mycotoxins from mould infested building materials

Only limited documentation of non-allergenic, especially toxic reactions after inhalation of microfungal spores in water damaged buildings exists. Recently attention has been drawn to the mycotoxins as causal compounds, as some the dominating genera found in buildings are well known mycotoxin producers.Penicillium chrysogenum and A. ustus do not seem to produce any known mycotoxins when growing on building materials, whereasP. brevicompactum produces mycophenolic acid, someP. polonicum produces verrucosidin and verrucofortine,A. versicolor produces sterigmatocystins,A. niger produces nigragillin, orlandin, naphtho-γ-pyrones and tetracyclic compounds, someA. ochraceus produces ochratoxin A,Alternaria spp. produce alternariol and alternariol monomethyl ether,Chaetomium globosum produce chaetoglobosins, and finally 30-40% ofStachybotrys chartarum isolates from buildings produce macrocyclic trichothecenes and a number of other biologically active compounds.

Synthesis based on cyclohexadienes. Part 35: Synthesis of some polyquinane derivatives

A new strategy for the synthesis of a [4.3.3]propellane derivative and an angular triquinane is described starting from the tetracyclic compounds 8 and 15. The synthesis of the [4.3.3]propellane involved a radical cyclisation and a Beckmann fragmentation as the key steps. The angular triquinane was synthesised employing an oxidative cleavage of the tetracyclic system. A novel Wilkinson’s catalyst-mediated carbon–carbon bond formation (12 → 30) is reported.

Tetracyclic polyprenoids: Indicators of freshwater (lacustrine) algal input

Because of the great variety of lacustrine-source depositional characteristics and biological consortia, identification of a universally applicable indicator of freshwater or brackish-water organic input for crude oils and rock extracts has proven elusive. Tetracyclic polyprenoid compounds (TPP) are present in relatively high concentrations in oils and associated source rocks deposited under freshwater or brackish-water conditions, but typically are present in relatively low concentrations in samples from marine or coal-forming depositional environments. A TPP ratio, constructed from the gas chromatography–tandem mass spectrometry peak areas of a C30 tetracyclic polyprenoid divided by the sum of the peak areas of the C26 27-norcholestanes, revealed great specificity in identifying freshwater or brackish-water algal input, particularly in crude oils.

The strategy for Co2(CO)8-catalyzed double carbonylative [2 + 2 + 1] cycloaddition or [2 + 2 + 2] cycloaddition reaction of triynes: a new synthetic method for tetracyclic compounds †

Download options Please wait... Supplementary files Spectroscopic data DOC (40K) Article information DOI https://doi.org/10.1039/A909605A Article type Communication Submitted 06 Dec 1999 Accepted 10 Dec 1999 First published 27 Jan 2000 Download Citation J. Chem. Soc., Perkin Trans. 1, 2000, 141-144 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions The strategy for Co2(CO)8-catalyzed double carbonylative [2 + 2 + 1] cycloaddition or [2 + 2 + 2] cycloaddition reaction of triynes: a new synthetic method for tetracyclic compounds S. U. Son, S. Paik, S. I. Lee and Y. K. Chung, J. Chem. Soc., Perkin Trans. 1, 2000, 141 DOI: 10.1039/A909605A To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Search articles by author Seung Uk Son Se-Jung Paik Sang Ick Lee Young Keun Chung

Fused Quinoline Heterocycles III: Synthesis of First Annulated 1,4,5,6,6a-Pentaazabenzo[a]indacenes, 1,3,5,6-tetraazaaceanthrylenes and 5,7,9,11-Tetraazabenzo[a]fluorenes

An easy and efficient synthesis of the versatile, hitherto unreported methyl 3-amino-4-chloro-1-ethyl-pyrrolo[3,2-c]quinoline-2-carboxylate (9) is described. Reaction of 9 with sodium azide gives the corresponding tetracyclic ring system 10 in near quantitative yield. With isothiocyanates 13a,b the corresponding new 1,3,5,6-tetraazaaceanthrylenes 14a and 14b are formed, respectively. Refluxing 9 with an excess of morpholine (15a) in boiling ethanol yields the corresponding pyrrolo[3,2-c]quinolines 16a which react with isothiocyanates 13a,c to afford the new 5,7,9,11-tetraazabenzo[a]fluorenes 17a,b. Refluxing 9 with an excess of butylamine affords the corresponding intermediate 16b, which reacts with ethyl chloroformate and triethyl orthoformate to furnish the novel 1,3,5,6-tetraazaaceanthrylenes 18 and 19, respectively. On the other hand, reacting 16b with acetic anhydride does not give the expected tetracyclic compound 20, but instead, the interesting pyrrolo[3,2-c]-quinolines 21 is obtained.