RESUMO
A ligand-free Ni(ii)-catalyzed cascade annulation reaction for the synthesis of 4-aryl-substituted isotetronic acids from 2-acetamido-3-arylacrylates via vinylic C-H functionalization is reported. The reaction proceeds through heteroatom guided electrophilic insertion of nickel to the vinylic double bond followed by annulation with dibromomethane. This unconventional route features cascade steps, sole product formation, multiple functional group tolerance, low cost of catalysts and reagents, and readily available starting materials. Using this method, various aryl-substituted isotetronic acids have been synthesized which are biologically relevant. The annulation of 2-acetamido-3-arylacrylates has also been assessed with 1,2-dichloroethane, which resulted in the rearranged annulated products of 5-methyl substituted isotetronic acids.
RESUMO
The reaction of 3-cyanophthalides with allene carboxylates in the presence of tBuOLi results in a tandem annulation furnishing naphtho[ b]furanones in good yields with no loss of carbon. The carbon economy is explained by a tandem process, in which the initially expelled cyanide induces the second annulation.
RESUMO
This study discloses an efficient synthetic route for the regiospecific construction of a C5 glycoside angucycline representative of mayamycin. The key steps are intramolecular aldol condensation and Hauser annulation, and the key precursor for the aldol reaction is accessible through utilization of α-lithiation of a vinyl ether.
Assuntos
Benzo(a)Antracenos/síntese química , Glicosídeos/síntese química , Benzo(a)Antracenos/química , Glicosídeos/química , Estrutura MolecularRESUMO
Hexa-2,5-dienoates, susceptible to isomerization by acids and bases, are suitable for the [4+2] anionic annulation to give 3-(2-alkenyl)naphthoates in regiospecific manner. When combined with intramolecular carbonyl-ene reaction (ICE), the accessibility of the naphthoates culminates in a new synthesis of anthraquinones and diastereoselective synthesis of tetrahydroanthraquinones. This strategy has also resulted in a 3-step synthesis of dehydroherbarin from a 3-methallylnaphthoate.
RESUMO
An efficient and regioselective synthetic route to naphthoquinone/naphthoquinol-carbohydrate hybrids has been developed. It is based upon anionic annulation of 3-nucleofugalphthalides with an acrylate appended sugar moiety. In each of the annulations studied, the arene-carbohydrate hybrids were obtained in good to excellent yields. The in vitro cytotoxic activity of the synthetic naphthoquinone/naphthonol-carbohydrate hybrids were evaluated against the human cervical cancer cell line (HeLa), and a few of them were found to exhibit potent anticancer activity against the cell line.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Carboidratos/química , Carboidratos/farmacologia , Naftoquinonas/química , Naftoquinonas/farmacologia , Ânions/síntese química , Ânions/química , Ânions/farmacologia , Antineoplásicos/síntese química , Carboidratos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Naftoquinonas/síntese química , Neoplasias/tratamento farmacológicoRESUMO
Allene carboxylates, scarcely used as Michael acceptors, serve as acceptors in the annulation with phthalides in the presence of LDA and provide a one-pot synthesis of naphtho[c]furanones in very good yields. This tandem annulation is proposed to proceed via transposition of the hydroxy group resulting from the initial annulation.
RESUMO
Dibromobenzoisofuranone 12, synthesized in six steps, was regiospecifically annulated with 5-substituted cyclohexenones 13/36 in the presence of LiOt-Bu to give brominated anthraquinones 14/38 in good yields. Darzens condensation of 30 was shown to give chain-elongated anthraquinone 32. Alkaline hydrolysis of 38 furnished 39 representing desulfoproisocrinin F.
RESUMO
Anionic annulations of 3-nucleofugal phthalides with α-alkyl(aryl)acrylates involving a demethoxycarbonylation provide a succinct synthesis of vitamin K and related naphthoquinones. Also reported is a new cascade reaction stemming from a Cope-retro-Wittig rearrangement. This cascade leads to direct formation of 1-hydroxy-4-prenyloxynaphthalene-2-carboxylates from the corresponding α-prenyl acrylate acceptors.
Assuntos
Naftoquinonas/síntese química , Vitamina K/análogos & derivados , Vitamina K/síntese química , Acrilatos/química , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química , Técnicas de Química Combinatória , Estrutura Molecular , Naftoquinonas/química , Estereoisomerismo , Vitamina K/químicaRESUMO
1-Hydroxycarbazole-2,3-dicarboxylates have been shown to undergo chemoselective reductive cyclization to furo[3,4-b]carbazolones on reaction with LiAlH4. One of the furocarbazolones is utilized to accomplish the first total synthesis of claulansine D and mafaicheenamine E in 9 and 6 steps respectively. The other key steps of the syntheses are addition of an allylic indium reagent and CC double bond isomerization.
Assuntos
Carbazóis/síntese química , Ácidos Carboxílicos/química , Lactonas/síntese química , Compostos de Alumínio/química , Carbazóis/química , Lactonas/química , Compostos de Lítio/química , Estrutura Molecular , EstereoisomerismoRESUMO
The anionic annulation of MOM-protected furoindolone with 4-bromoquinoline followed by deprotection of the N-MOM group provides calothrixin B, whereas that with 3-bromoquinoline yields isocalothrixin B. The outcomes are explained by the divergence of the reaction mechanism from commonly perceived quinolyne intermediate. A sequence of addition-cyclization-elimination is proposed to account for the formation of calothrixin from 4-bromoquinoline.
Assuntos
Alcaloides Indólicos/síntese química , Cristalografia por Raios X , Ciclização , Alcaloides Indólicos/química , Modelos Moleculares , Estrutura Molecular , EstereoisomerismoAssuntos
Benzofuranos/síntese química , Ftalimidas/síntese química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Benzoatos/química , Benzofuranos/classificação , Benzofuranos/farmacologia , Produtos Biológicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Ciclização , Lactonas/química , Oxirredução , Ftalimidas/classificação , Ftalimidas/farmacologiaRESUMO
This study discloses a general and convergent route for the regio- and stereospecific construction of the C5 glycosyl angucycline framework of mayamycin. C-Glycosidation, dearomatization, and Hauser annulation are the key steps. The synthetic analogues show cytotoxicity against different human cancer cell lines with IC50 values between 16.4 and 1.2 µM.
Assuntos
Benzo(a)Antracenos/síntese química , Glicosídeos/síntese química , Benzo(a)Antracenos/química , Linhagem Celular Tumoral , Glicosídeos/química , Humanos , Concentração Inibidora 50 , Estrutura Molecular , EstereoisomerismoRESUMO
The first total synthesis of chlorocyclinone A (1) is regioselectively completed in 28 steps. The key steps are Pd-catalyzed methoxycarbonylation, unprecedented Hauser annulation, Krohn photo-oxidation, and regioselective gem-dichlorination.
Assuntos
Antraquinonas/química , Antraquinonas/síntese química , PPAR gama/antagonistas & inibidores , PPAR gama/química , Paládio/química , Catálise , Estrutura Molecular , Oxirredução , EstereoisomerismoRESUMO
Arenes, heteroarenes, 1,3-dicarbonyls and organosilicon nucleophiles undergo highly efficient alkylation with allylic, propargylic and benzylic alcohols in the presence of a new 'Pd-Sn' bimetallic catalyst in nitromethane; water being the sole byproduct. The plausible mechanism of alkylation and the intermediacy of ether has been enumerated.
RESUMO
2-Azidoacrylates undergo [4+3] annulation with phthalides under anionic conditions at low temperatures to furnish 5-hydroxy-2-benzazepinones, the formation of which represents a new concept for the construction of azepines as well as a new reactivity of 2-azidoacrylates.
Assuntos
Acrilatos/química , Benzazepinas/química , Benzazepinas/síntese química , Técnicas de Química Sintética/métodos , Estereoisomerismo , Especificidade por SubstratoRESUMO
The synthesis of stilbenoids and styryl carboxylic acids is accomplished with high E-stereoselectivity by olefination of aldehydes with thiophthalides under basic conditions. The olefination is highly atom-efficient as it only loses elemental sulfur during the reaction. This olefination, in conjunction with retro Kolbe-Schmitt reaction, allows facile synthesis of E-hydroxystilbenoids with minimal employment of protecting groups. This study also discloses two important findings: formation of i) 4-methylsulfanyl isocoumarins and ii) an 2-arylindenone.
Assuntos
Benzofuranos/química , Estilbenos/química , Estirenos/síntese química , Compostos de Sulfidrila/química , Aldeídos/química , Alcenos/química , Hidroxilação , Modelos Moleculares , Estrutura Molecular , EstereoisomerismoRESUMO
The annulation of phthalides with α-alkyl/arylacrylates in the presence of LDA/LHMDS is shown to directly give alkyl/aryl-1-naphthols. The method involving a novel dealkoxycarbonylation obviates the regiochemical issues in the synthesis of polysubstituted naphthalenes, and it forms the key step in a three-step total synthesis of arnottin I, a naphthobenzopyranone natural product.
Assuntos
Cumarínicos/química , Cumarínicos/síntese química , Naftóis/química , Naftóis/síntese química , Acrilatos/química , Benzofuranos/química , Estereoisomerismo , Especificidade por SubstratoRESUMO
The key prenylcarbazole precursor 33 was readily assembled from diester 30 by an ester-driven para-Claisen rearrangement followed by selective removal of the ester function. Unusual oxidative cyclization of 33 by m-CPBA resulted in the total synthesis of tetracyclic carbazole natural products 3 and 11.
Assuntos
Alcaloides/síntese química , Carbazóis/química , Alcaloides/química , Carbazóis/síntese química , Ciclização , OxirreduçãoRESUMO
The first total synthesis of euplectin, a rare metabolite with a chromone annulated indenone motif, has been accomplished in 17 steps. This has been possible through interplay among three key reactions: a Hauser sulfoxide annulation, a new chromone formation and a late-stage retro-Diels-Alder reaction. The entire regiochemical integrity of the successful route is established by an iodine-catalyzed aromatization of a cyclohexane-1,3-dione and the Hauser annulation.
Assuntos
Fatores Biológicos/síntese química , Cromonas/química , Indenos/química , Fatores Biológicos/química , Estrutura Molecular , EstereoisomerismoRESUMO
The epoxyquinones (e.g., 24), readily assembled in one step from the quinols (e.g., 27) by a simplified version of the Dowd oxidation, are shown to undergo rearrangement to pyranonaphthoquinones (e.g., 28) and their ring contracted homologues (e.g., 29) on flash vacuum pyrolysis at 450 degrees C and 0.01 Torr. The rearrangement has been demonstrated to be useful for a regiospecific synthesis of lambertellin (3). Similarly, the masked aziridinocyclopentanone 9 rearranges to 2-pyridone (37).