Pentacyclic Ketone Research Articles

Isoindolin-1-ones from the stems of Nicotiana tabacum and their antiviral activities

In previous studies, several isoindolin-1-one analogs that exhibited significant anti-tobacco mosaic virus (anti-TMV) activities were isolated from Nicotiana tabacum. Since gene-editing mutants provide a new sample for the discovery of active metabolites, we focused on the stems of YN-18-23 (a mutant N. tabacum for gene editing with the alkaloid metabolic pathway cultivated by Yunnan Tobacco Company), which led to the isolation of four new (1-4) and four known (5-8) isoindolin-1-ones. To the best of our knowledge, nicindole C (3) is the first subclass of isoindolin-1-one bearing a pentacyclic ketone, while nicindole D (4) is the first example of isoindolin-1-one bearing a methyl-pyridin-2-(1H)-one moiety. Compounds 1-4 were tested for their anti-TMV activities, and the results revealed that compounds 1, 3, and 4 exhibited high anti-TMV activities at concentrations of 20μM with inhibition rates of 48.6, 42.8, and 71.5%, respectively. These rates are higher than the inhibition rate of the positive control (33.2%). The mechanistic study of compound 4, which had the highest anti-TMV activity revealed that increased potentiation of defense-related enzyme activities and downregulation of expression of the NtHsp70 protein may induce resistance in tobacco against the viral pathogen TMV. Molecular docking studies also revealed that the isoindolin-1-one substructure is fundamental for anti-TMV activity. The methyl-pyridin-2-(1H)-one moiety in compound 4 and the 2-oxopropyl groups in compounds 1 and 3 at the N-2 position may increase inhibitory activities. This study of the structure-activity relationship is helpful for finding new anti-TMV activity inhibitors. To study whether the isoindolin-1-ones have broader antiviral activities, compounds 1-4 were also tested for their anti-rotavirus activities. Compound 4 exhibited high anti-rotavirus activity with a therapeutic index (TI) value of 20.7. This TI value is close to that of the positive control (20.2).

Oxygen-containing organic compounds of the bituminous components of high-moor peat from the south of Western Siberia

The composition of the bituminous components of high-moor peats from the south of West Siberia (Tomsk oblast, Temnoe bog) was analyzed. The similarity of the compositions of fatty acids, n-alkan-2-ones, n-aldehydes, tetra- and pentacyclic ketones, esters, and aromatic alcohols in all of the test peat samples was found. At the same time, the total concentration of alkanones, which prevailed among the oxygen-containing organic compounds in raised bog peats, was small in floating bog peats. The peats of the floating bog section were differed from the raised bog peats in the composition of pentacyclic alcohols, which included compounds from the lupene group in addition to oleanene derivatives. Tetracyclic alcohols in floating bog peats mainly consisted of saturated structures, whereas raised bog peats contained exclusively unsaturated stenols. The differences in the concentrations and composition of fatty acids, acyclic ketones, aldehydes, esters, steroids, and terpenoids observed in peats from two sections of the Temnoe bog mainly depend on the conditions of peat buildup and burial.

ChemInform Abstract: Synthesis of Ring D Modified Morphinan Systems via Ring Expansion of a Key Codeine Intermediate.

Ring expansion and ring fragmentation products were synthesized from pentacyclic ketones 3 and 4 via Baeyer−Villiger oxidation. Oxidation of 3 with m-chloroperbenzoic acid afforded δ-lactone 9 whic...

Total Synthesis of (±)- and (−)-Actinophyllic Acid

Development of efficient sequences for the total syntheses of (+/-)-actinophyllic acid (rac-1) and (-)-actinophyllic acid (1) are described. The central step in these syntheses is the aza-Cope/Mannich reaction, which constructs the previously unknown hexacyclic ring system of actinophyllic acid in one step from much simpler tetracyclic precursors. The tetracyclic hexahydro-1,5-methano-1H-azocino[4,3-b]indole ketone rac-37 is assembled from o-nitrophenylacetic acid in four steps, with oxidative cyclization of a dienolate derivative of tricyclic precursor rac-35 being the central step. In the first-generation synthesis, this intermediate is transformed in two steps to homoallyl amine rac-43, whose formaldiminium derivative undergoes efficient aza-Cope/Mannich reaction to give pentacyclic ketone rac-44. In four additional steps, this intermediate is advanced to (+/-)-actinophyllic acid. The synthesis is streamlined by elaborating ketone rac-37 to beta-hydroxyester intermediate rac-53, which is directly transformed to (+/-)-actinophyllic acid upon exposure to HCl and paraformaldehyde. This concise second-generation total synthesis of (+/-)-actinophyllic acid is realized in 22% overall yield from commercially available di-tert-butyl malonate and o-nitrophenylacetic acid by a sequence that proceeds by way of only six isolated intermediates. The first enantioselective total synthesis of (-)-actinophyllic acid (1) is accomplished by this direct sequence from tricyclic keto malonate (S)-35. Catalytic enantioselective reduction of alpha,beta-unsaturated ketone 66 is the key step in the preparation of intermediate (S)-35 from the commercially available Boc-amino acid 65. Discussed also is the possibility that the aza-Cope/Mannich reaction might be involved in the biosynthesis of (-)-actinophyllic acid.

Pentacyclic triterpenoid ketones in peat from Gannan Marsh, China

Abundant terrigenous triterpenoid ketones and a series of hopanoid ketones were detected in a peat sample from the recent Gannan Marsh. The identifications of pentacyclic triterpenoid ketones are discussed in detail. Based on the compositional features of pentacyclic triterpenoid ketones in the sample, it is proposed that terrigenous triterpenoid kentones originate directly from organisms or are diagenetic oxidation products of their alcohols, and hopanoid ketones are formed from hopanoids (e.g. hopanoid alcohols and hopenes) by chemical and biochemical processes. These data provide evidence for the applied studies of pentacyclic triterpenoid ketones as biomarker compounds.

Synthesis of ring D modified morphinan systems via ring expansion of a key codeine intermediate

Ring expansion and ring fragmentation products were synthesized from pentacyclic ketones 3 and 4 via Baeyer-Villiger oxidation. Oxidation of 3 with m-chloroperbenzoic acid afforded delta-lactone 9 which was transformed to enone 12 en route to the C6 inverted ether 14. Analogous oxidation of 4 gave delta-lactone 18. Opening of the lactone ring of 14 and 18 led to seco structures which, in the case of 19, underwent reannulation with incorporation of nitrogen to yield the hydroxylactam 21.

Anionic [4+2] cycloaddition strategy to linear furocoumarins: Synthesis of 8-methoxypsoralen and its isoster

The sulfoxide esters 14 and 20d are successfully annulated with bicyclic enone 8 in the presence of tBuOLi to provide the pentacyclic ketones 9a and 21a respectively in good yields (≥70%). Flash vacuum pyrolysis of O-methyl derivatives 9b and 21b at ∼ 500° C/. 1 mm provide furoindacenones 16b and 22b respectively, which in turn are convertible to furocoumarins 1 and 3.

Nucleophilic additions to 4-substituted snoutanones: getting a measure of long range electrostatic and orbital control of π-face selectivity

Pentacyclic ketones 10a–e (snoutan-9-ones) undergo nucleophilic additions with the same facial preference as the corresponding norsnoutanones 9a–e, but with markedly reduced selectivity, revealing the involvement of electrostatic effects in the former and implying the importance of hyperconjugative orbital interactions in determining π-face selectivity in the latter systems.

Molybdenum‐Catalysed and ‐Mediated Cycloaddition Reactions: Efficient Synthesis of Complex Products from 1‐Oxa‐1,3‐dienes and Cyclotrienes or ‐tetraenes

AbstractMolybdenum‐mediated [6 + 2]‐cycloaddition reactions of unsaturated ketones to cyclotri‐ or ‐tetraenes, e.g. cyclohepta‐1,3,5‐triene or cyclooctatetraene, proceed under very mild conditions, in high yields and with excellent stereoselectivity starting from the appropriate dicarbonylbis[π4‐(1‐oxa‐1,3‐diene)]molybdenum complexes. The stereochemistry of the product arising from the reaction of dicarbonylbis[π4‐(5‐methylhex‐3‐en‐2‐one)]molybdenum with cyclohepta‐1,3,5‐triene allows one to deduce a stepwise mechanism for this addition. The reactants are fused, as would be expected from an exo‐type approach, thus indicating an intermolecular attack of the cycloheptatriene. Tungsten oxadiene complexes are effective in analogous reactions at somewhat reduced reaction rates. Catalytic cycloadditions are observed in several cases when 1–5 mol% of the highly reactive dicarbonylbis[π4‐(R‐(+)‐pinocarvone)]molybdenum is employed as the catalyst. Cycloadducts are formed diastereospecifically in most cases. When cyclooctatrienes are employed as reactants, a sequence of electrocyclization of the triene and subsequent [4 + 2]‐cycloadditon occurs with high selectivity and efficiency, leading to a pentacyclic ketone. The product structure reveals an endo‐type approach of the polyene in this case.

Syntheses of Strychnos and Aspidospermatan-Type Alkaloids. 8. Selective Total Syntheses of Mossambine and 14-epi-Mossambine by a Radical Cyclization Reaction(1).

Mossambine (6) was obtained by a six-step reaction sequence from the indoloazepine ester 7. Radical cyclization of the tetracyclic vinyl iodide 12a provided a racemic pentacyclic ketone 16E, which could be converted to either enantiomer by condensation with (S or R)-N,S-dimethyl-S-phenylsulfoximine and selective pyrolysis of the resulting diastereomeric alcohols 18 and 19 or 20 and 21. Selective reductions of the resolved (or racemic) ketone 16E provided mossambine (6) and its hydroxy epimer 17.

A Molybdenum‐Catalysed Electrocyclisation‐Cycloaddition Sequence: Synthesis and Structure of a Pentacyclic Unsaturated Ketone

The pentacyclic unsaturated ketone 3 is obtained as the sole product by the reaction of pinocarvone (1) with cycloocta-triene in the presence of catalytic amounts of dicarbonyl-bis(η4-pinocarvone)molybdenum (2). Compound 3 formally resulting from a [4 + 2] cycloaddition reaction of bicy-clo[4.2.0]octa-2,4-diene with the alkene fragment of pinocarvone was characterised by means of spectroscopy (1H, 13CNMR, IR, MS) as well as by X-ray crystal structure analysis. A mechanism is proposed involving rigid molybdenum complexes as intermediates in order to explain the stereospecificity of the reaction.

A twisted pentacyclic ketone derivative

exo-11-Methoxy-9-methylpentacyclo[6.3.1.0 3,10 . 4,12 .O 5,9 ]dodecan-2-one (1), C 14 H 18 O 2 , M r =218.30, orthorhombic, Pbca, a=7.288 (1), b=12.432 (3), c=24.392 (2) A, V=2209.88 A 3 , Z=8, D x =1.311 g cm -3 , λ(Cu Kα)=1.54056 A, μ=6.425 cm -1 , F(000)=944, T=148 K, R=0.0547 and wR=0.0552 for 1602 unique reflections. The molecule consists of a «twisted» pentacyclic hydrocarbon ring system with methyl and methoxy substituents and a ketone functional group

An asymmetric route to the demethoxy-fumitremorgins

By use of a modified Pictet–Spengler reaction under conditions of kinetic control, the optically pure cis-1,3-disubstituted tetrahydro-β-carboline 21a was prepared from L-tryptophan; this generated a key tricyclic unit that possessed the correct relative and absolute stereochemistry for transformation into demethoxy derivatives of the fumitremorgin mycotoxins. In particular, we converted 21a into the pentacyclic ketone 29, whose structure was confirmed by X-ray crystallography; and 29 was further transformed into demethoxy-fumitremorgin C 1b, whose NMR data matched that of the natural product 1a extremely closely. Our methodology also gives access to a range of analogues of the fumitremorgins.

A new synthetic route to vindorosine

The pentacyclic ketone (6), a direct precursor of vindorosine (1b), has been synthesised with an overall yield of 41%, by a six-step sequence involving a Diels–Alder reaction, stereospecific alkylation, and Pummerer rearrangement coupled with electrophilic cyclisation.

Methylierung von 4‐Hydroxy‐4‐(2‐piperidyl)‐4H‐pyrazolo [1,5‐a]indol mit Formaldehyd und Ameisensäure. 11. Mitteilung über metallorganische Reaktionen und Folgeprodukte

AbstractIn the 10th communication of this series [1] the synthesis of 4‐hydroxy‐4‐(2‐piperidyl)‐4H‐pyrazolo[1,5‐a]indole (4) was described (Scheme). Surprisingly enough, methylation of this compound with formaldehyde and formic acid led via ring closure and a subsequent rearrangement to a pentacyclic ketone. By means of 13C‐NMR.‐spectroscopy and mass spectroscopy, this ketone could be identified as a indolizino‐pyrazolo‐indole (9). Its structure and configuration were determined by X‐ray structure analysis.

Photochemie von tricyclischen β, γ‐γ′, δ′‐ungesättigten Ketonen. 50. Mitteilung über Photoreaktionen

Photochemistry of tricyclic β, γ‐γ′, δ′‐unsaturated ketonesThe easily available tricyclic ketone 1 (cf. Scheme 1) with a homotwistane skeleton yielded upon direct irradiation the cyclobutanone derivative 3 by a 1,3‐acyl shift. Further irradiation converted 3 into the tricyclic hydrocarbon 4. However, acetone sensitized irradiation of 1 gave the tetracyclic ketone 5 by an oxa‐di‐π‐methane rearrangement. Again with acetone as a sensitizer the ketone 5 was quantitatively converted to the pentacyclic ketone 6. The conversion 5 → 6 represents a novel photochemical 1,4‐acyl shift. The possible mechanisms are discussed (see Scheme 7). The tricyclic ketone 2 underwent similar types of photoreactions as 1 (Scheme 2). Unlike 5 the tetracyclic ketone 9 did not undergo a photochemical 1,4‐acyl shift. The epoxides 10 and 14 derived from the ketones 1 and 2, respectively, underwent a 1,3‐acyl shift upon irradiation followed by decarbonylation, and the oxa‐di‐π‐methane rearrangement (Schemes 3 and 4). The diketone 18 derived from 1 behaved in the same way (Scheme 5). The tetracyclic diketone 21 cyclized very easily to the internal aldol product 22 under the influence of traces of base (Scheme 5). Upon irradiation the γ, δ‐unsaturated ketone 24 underwent only the Norrish type I cleavage to yield the aldehyde 25 (Scheme 6).

Zur Bildung polycyclischer Ketone bei der Umsetzung von 5, 6‐Dimethyliden‐bicyclo[2.2.1]hept‐2‐en mit Dieisen‐enneacarbonyl

On the Formation of Polycyclic Ketones in the Reaction of 5, 6‐Dimethylidene‐bicyclo[2.2.1]hept‐2‐ene with Diiron‐enneacarbonyl5,6‐Dimethylidene‐bicyclo[2.2.1]hept‐2‐ene (4), in the presence of diiron‐ennea‐carbonyl in boiling hexane, produces the endo‐and exo‐tricarbonyl‐iron complex of 4 (endo‐ and exo‐5). A mixture of numerous tricarbonyl‐iron complexes with ligands derived from coupling and carbonylation reactions of 4 are also formed. The endo‐ and exo‐5 compounds as well as two tricarbonyl‐iron complexes (7 and 8) of penta‐cyclic ketones could be isolated and characterized. After oxidative removal of the tricarbonyl‐iron groups in the reaction mixture the three pentacyclic ketones 9, 10 and 11 were separated. Structure and configuration of these ketones were deduced from spectroscopic analyses, especially from their 1H‐ and 13C‐NMR. spectra (see tables 1–4). Whereas the symmetric pentacyclic ketone 11 is of a known type (cf. [1]) the two spiroketone 9 and 10 represent compounds of a new type. Their structure and configuration shows that in ironcarbonyl induced thermal cyclopentanone formations, an exocyclic double bond can also take part.

Umwandlung von 6‐Methyliden‐tricyclo[3.2.1.02,7]oct‐3‐en‐8‐onen in Norcaradien/Cycloheptatrien‐Derivate

Transformation of 6‐Methyliden‐tricyclo[3.2.1.02,7]oct‐3‐en‐8‐ones into Norcaradiene/Cycloheptatriene‐Derivatives.Tricyclic ketones of type 1,5‐dimethyl‐6‐methyliden‐tricyclo[3.2.1.02,7]oct‐3‐en‐8‐one (1) [1] rearrange on heating with sodium methylate mainly to methyl‐7‐methyl‐bicyclo[4.1.0]hepta‐2,4‐dien‐7‐carboxylates = methyl‐7‐methyl‐norcaradien‐7‐carboxylates (4). Moreover, the formation of methyl 2‐aryl‐propionate (5) is observed. Thus, tricyclic 1 gives a mixture of norcaradiene derivatives 2 and 4 in 50% yield together with 13% of methyl 2‐(2′, 3′‐dimethylphenyl)‐propionate (5) (Scheme 1). Similarly the tricyclic ketone 7 rearranges to norcaradienes 8 and 9 (31,5%) and methyl 2‐(2′, 3′, 5′‐trimethylphenyl)‐propionate (10, 4%). In this case, the reduction products of 7, i.e. the alcohols 11 (24%) and 12 (8%) as well as other products derived from 11 are observed; heating of the endo‐alcohol 11 with sodium methylate leads to the 2‐arylpropan‐1‐ols 13 and 14 (Scheme 2). Under the same conditions the ketone 18 affords the norcaradiene ester 20 (Scheme 3). Scheme 4 shows the rearrangement of the pentacyclic ketone 21 to the cycloheptatriene derivative 22 and the base catalysed isomerisation of 22 to 23.The structure elucidations were achieved with the help of UV.‐, IR.‐ and mainly NMR. spectra. The carboxy or methoxycarbonyl group assumes the exo‐position in all the norcaradiene derivatives (NMR., also in the presence of NMR. shift reagents). The cycloheptatriene‐noncaradiene‐equilibrium is shifted to the norcaradiene side to > 95% in compounds 2, 4, 8 and 9 and to > 90% in 19 and 20. This is due to the 7‐exo‐carboxy or 7‐exo‐methoxycarbonyl group and the methyl groups in positions 2 and 3 (cf. Klärner [9], chapter 4). On the other hand, in the case of 22 the cycloheptatriene structure is almost exclusively predominant.The most probable mechanism for the rearrangement of tricyclic ketones of type 1 to methylnorcaradien‐7‐exo‐carboxylates or to the corresponding carboxylic acids is depicted in Scheme 5. Thus, the reaction path leads from 1 through a, c, f, g and h to 4. The aromatization reaction of 1 to 5 and 3 proceeds preferentially through a, c (Scheme 5) and k (Scheme 6). The conversation of the tricyclic endo‐alcohol 11 to 2‐aryl‐propan‐1‐ols 13 and 14 using sodium methylate occurs to ca. 90% via m → n and ca. 10% via m → p (Scheme 7); the primarily formed 2‐aryl‐propanals are reduced under the reaction conditions. The exo‐isomer 12 shows no similar reaction.

2-(2-Naphthyl)benzo[b]thiophen. Part IV. Further aspects of electrophilic substitution, and ring closures to yield pentacyclic derivatives

Electrophilic reagents attack 2-(2-naphthyl)benzo[b]thiophen at the free position on the thiophen ring, but there does not seem to be any strongly preferred position for further electrophilic substitution. Attempts to decarboxylate 2-(1-nitro-2-naphthyl)benzo[b]thiophen-3-carboxylic acid produced internal nucleophilic displacement of the nitro-group to yield a pentacyclic lactone. A pentacyclic ketone and a pentacyclic phenol have been prepared by Friedel–Crafts ring closures between the benzo[b]thiophen and naphthalene ring systems. A direct synthesis of the title compound is reported.

ChemInform Abstract: INTRAMOLECULAR KETO‐CARBENOID ADDITION TO DOUBLE BONDS, STEREOCHEMISTRY OF THE CATALYTIC REDUCTION OF DELTA(9(11))‐GIBBENES AND RELATED COMPOUNDS

AbstractDie Belichtung der Diazoketone (I) und (IV) in Cyclohexan/Tetrahydrofuran in Gegenwart eines aktivierten CuO‐Katalysators ergibt die Cyclopropane (II) bzw. (V).