Toward new camptothecins. Part 5: On the synthesis of precursors for the crucial Friedländer reaction

The synthesis of potential precursors of ketones, which could be used to obtain camptothecin analogs, is described. Noteworthy is the difference of reactivity between indolizinone and pyrrolidinoquinazolinone heterocycle.     

Synthesis and characterization of quinoline derivatives via the Friedländer reaction

A rapid and efficient method for the synthesis of various poly-substituted quinolines has been developed via the Friedländer condensation of 2-aminoarylaldehyde with a carbonyl compound containing a reactive α-methylene group in the presence of sodium ethoxide (10 mol %). The new tetrahydroacridine derivatives and 11H-indeno[1,2-b]quinolines were synthesized in high yield with sodium ethoxide as a catalyst via the Friedländer reaction. The conditions of reaction were discussed and the possible reaction mechanism was proposed.     

Toward new camptothecins. Part 7: Synthesis of thioluotonin and its 5-methoxycarbonyl derivative

The synthesis of thiodeoxyvasicinone and thioluotonin derivatives is described. The results obtained indicate that in these series, oxygen to sulfur replacement leads to absence of strong interaction with topoisomerase I-DNA.     

Photoactive amorphous molecular materials based on quinoline amines and their synthesis by Friedländer condensation reaction

A new class of conjugated quinoline amines was prepared by Friedländer condensation reaction. They showed stable amorphous state below glass transition temperatures as examined by differential scanning calorimetry and X-ray diffraction studies. Additionally, they exhibited fluorescence properties in the blue to green region of visible spectrum in both solution and solid state. Their fluorescence quantum efficiencies in chloroform were in a broad range of 3-45%. Interestingly, they formed stable fibers with micrometer thickness drawn from melt, which were characterized by polarizing optical microscopy and scanning electron microscopy studies.     

Towards new camptothecins. Part 3: Synthesis of 5-methoxycarbonyl camptothecin

The synthesis of two camptothecin analogs substituted by a carbonyl function on position 5 of cycle C was realized. New conditions were studied to obtain the E-lactone ring of these heterocycles. These compounds were obtained from the reaction of Bredereck's reagent with indolizines derived from pyroglutamic acid. This yielded dimethylaminovinyl groups whose oxidation by NaIO₄ yielded ketones. The indolizinones obtained were reacted in Friedlander condition, to give the scaffold of the desired camptothecins.     

Toward new camptothecins. Part 4: On the reactivity of nitro and amino precursors of aza analogs of 5-methoxycarbonyl camptothecin

In the context of formation of new aza analogs of camptothecin, nitration then reduction of condensed pyridones was realized, leading to new derivatives of pyrrolo-aza-indoles. Treatment of these compounds with hydrobromic acid led to new structure rearrangements while oxidation of the α-position was unsuccessful. Mechanisms of formation of the new products are discussed.     

Synthesis of new difluoroalkyl propargylic ketones and their use for the preparation of fluorinated heterocycles

Synthetic methodology studies are reported towards the preparation of new propargylic ketones with CF₂R side chains. These molecules are used for the synthesis of various types of five- or six-membered heterocycles with difluoroalkyl side chains.     

Synthesis of new carbohydrate-derived ketones as organocatalysts in the enantioselective epoxidation of arylalkenes. Part 2: Chiral ketones from sugars

A range of new, somewhat complex, stereochemically varied, and structurally related carbohydrate-derived ketones were synthesised by a simple method from the carbohydrate precursor (d-gluco and d-galacto derivatives). The common skeleton possesses the keto function sited on a seven-membered ring fused to positions 2 and 3 of the sugar moiety. Their chirality transfer capability in the dioxirane-mediated epoxidation of arylalkenes was evaluated.     

Towards new camptothecins. Part 2: Synthesis of the ABCD ring scaffold substituted by a carboxyl group in the 5-position

In the context of formation of camptothecins substituted by a carbonyl function on position 5 of cycle C, synthesis of a new keto tetrahydroindolizine was realized. This compound was obtained from the reaction of Bredereck's reagent with an indolizine derived from pyroglutamic acid. That yielded a dimethylaminovinyl group whose NaIO₄ oxidation gave a ketone. The indolizinone obtained was reacted in Friedlander condition to give the ABCD ring scaffold of camptothecins substituted by a methoxycarbonyl group on the 5-position. It was also shown that, if it is desired, a 5-carboxamide group does not need to be introduced at the beginning of the synthesis sequence.     

Aziridinyl ketones and their cyclic anils. 6. Proton-acceptor capacities of aziridinyl ketones

The proton-acceptor capacities of a number of cis- and trans-aziridinyl ketones were estimated by IR spectrometry from the shifts of the OH bands of phenol, p-bromophenol, and trichloroacetic acid.It is shown that the cis isomers interact with all of the proton donors, whereas the trans isomers interact only in CCl₃COOH.The latter is due to the fact that a strong intramolecular hydrogen bond exists in the trans-NH-aziridinyl ketones, whereas considerable steric hindrance to complexing develops in the trans-N-alkylaziridinyl ketones.It was established that the formation of complexes takes place at the carbonyl group of the aziridinyl ketones.See [1] for Communication 5.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1641–1644, December, 1981.     

1,2-联烯基酮的合成与反应

1,2-联烯基酮可以通过2-丙炔基酮异构化反应,相应有机金属试剂中间体与酯、酰氯或酰胺的反应,[2,3]或[3,3]迁移反应,Wittig反应,消除反应,2,3-联烯醇氧化等方法合成。由于联烯酮上含有吸电子基团羰基,它可发生亲核加成、环加成、环化反应。     

Synthesis and some chemical properties of the 6-arylsulfonyl-6-polyfluoroalkanoyl-5,6-dihydro-2H-thiins—new fluorine-containing ketones

1,1-Dihydro-1-tolylsulfonyl polyfluoroalkan-2-ones react with phthalimidosulfenyl chloride to form sulfenylated products on the active methylene group, 1-phthalimidothio-1-tolylsulfonyl polyfluoroalkan-2-ones. Decomposition of the latter leads to formation of 1-thioxo-1-tolylsulfonyl polyfluoroalkan-2-ones. These compounds undergo easily the hetero Diels-Alder reaction with electron-rich 1,3-dienes as dienophiles to give polyfluoroalkanoyl substituted derivatives of 5,6-dihydro-2H-thiins. 6-Arylsulfonyl-6-polyfluoroalkanoyl-5,6-dihydro-2H-thiins obtained react with alkali to give 5,6-dihydro-6-p-tolylsulfonyl-2H-thiins and with methanol to give 2-polyfluoroalkanoyl-6H-thiins.     

Friedländer reaction of 3-acetyltropolone: Synthesis of 3-(2-quinolyl)tropolones

3-Acetyltropolone ( 1a ) reacted with 2-aminobenzaldehydes in the presence of sodium ethoxide to afford 3-(2-quinolyl)tropolone ( 3aa ) in 96% yield. Methyl- and isopropyl-substituted tropolones 1b,c also gave six 3-(2-quinolyl)tropolones in excellent yields. The compound 3aa was allowed to stand in 40% aqueous methylamine solution to give 7-methylamino-2-(2-quinolyl)tropone ( 4 ).     

Synthesis of β-mercuri ketones by the reaction of siloxycyclopropanes with mercuric acetate and their conversion to α-methylene ketones and γ-ketoesters

Siloxycyclopropanes were quantitatively converted to β-acetoxymercuri ketones by the reaction with mercuric acetate. Successive treatment with palladium chloride or palladium chloride/carbon monoxide gave α-methylene ketones or γ-ketoesters, respectively, in good yields.     

o-Benzenedisulfonimide as a reusable Brønsted acid catalyst for an efficient and facile synthesis of quinolines via Friedländer annulation

The synthesis of quinolines via Friedländer annulation was carried out in the presence of catalytic amount of o-benzenedisulfonimide as Brønsted acid organocatalyst; the reaction conditions were mild and the yields of the target products were good. The organocatalyst was easily recovered and purified, ready to be used in further reactions.     

Synthesis of substituted tryptamines and their homologs: A new aspect in the Fischer reaction

A number of cyclic imines and amino ketones were studied as the starting material for indole synthesis. Amino ketone arylhydrazones are key intermediates undergoing the Fischer rearrangement; the possibility of the reaction is determined by the structure of an amino carbonyl compound. A convenient one-step method for the synthesis of indolylalkylamines allowed tryptamines and their homologs to be obtained in high yields. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1186–1194, May, 2005.     

Synthesis of new NHC-rhodium and iridium complexes derived from 2,2′-diaminobiphenyl and their catalytic activities toward hydrosilylation of ketones

Four new N-heterocyclic carbene (NHC)-rhodium and iridium complexes derived from 2,2′-diaminobiphenyl have been successfully synthesized and their structures have been unambiguously characterized by X-ray diffraction. Their catalytic activities for hydrosilylation of ketones with diphenylsilane were investigated. It was found that NHC-rhodium complex (6) is the best one among the four catalysts for the reduction of ketones.     

Synthesis of new polyaza heterocycles. Part 42: Diazines

Using Pd-catalyzed Stille cross-coupling reactions, we report here the synthesis of various mono- or bis(tri-n-butylstannyl)diazines which were reacted with various halogenated diazines to access to various polyaza heterocyclic derivatives.     

Versatility of the Biginelli reaction: Synthesis of new biphenyl dihydropyrimidin-2-thiones using different ketones as building blocks

A multi-component synthesis of biphenyl dihydropyrimidin-2-thiones from 1-phenylthiourea, aldehydes and ketones or di-ketones has been demonstrated. The reaction proceeded well for aldehydes with electron donor or acceptor substituents under mild conditions.