RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
Asunto(s)
Benzo(a)Antracenos/síntesis química , Glicósidos/síntesis química , Benzo(a)Antracenos/química , Glicósidos/química , Estructura MolecularRESUMEN
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.
RESUMEN
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.
RESUMEN
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.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Carbohidratos/química , Carbohidratos/farmacología , Naftoquinonas/química , Naftoquinonas/farmacología , Aniones/síntesis química , Aniones/química , Aniones/farmacología , Antineoplásicos/síntesis química , Carbohidratos/síntesis química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Naftoquinonas/síntesis química , Neoplasias/tratamiento farmacológicoRESUMEN
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.
RESUMEN
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.
Asunto(s)
Carbazoles/síntesis química , Ácidos Carboxílicos/química , Lactonas/síntesis química , Compuestos de Aluminio/química , Carbazoles/química , Lactonas/química , Compuestos de Litio/química , Estructura Molecular , EstereoisomerismoRESUMEN
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.
Asunto(s)
Alcaloides Indólicos/síntesis química , Cristalografía por Rayos X , Ciclización , Alcaloides Indólicos/química , Modelos Moleculares , Estructura Molecular , EstereoisomerismoRESUMEN
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.
Asunto(s)
Benzo(a)Antracenos/síntesis química , Glicósidos/síntesis química , Benzo(a)Antracenos/química , Línea Celular Tumoral , Glicósidos/química , Humanos , Concentración 50 Inhibidora , Estructura Molecular , EstereoisomerismoRESUMEN
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.
Asunto(s)
Antraquinonas/química , Antraquinonas/síntesis química , PPAR gamma/antagonistas & inhibidores , PPAR gamma/química , Paladio/química , Catálisis , Estructura Molecular , Oxidación-Reducción , EstereoisomerismoRESUMEN
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.
RESUMEN
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.
Asunto(s)
Benzofuranos/química , Estilbenos/química , Estirenos/síntesis química , Compuestos de Sulfhidrilo/química , Aldehídos/química , Alquenos/química , Hidroxilación , Modelos Moleculares , Estructura Molecular , EstereoisomerismoRESUMEN
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.
Asunto(s)
Cumarinas/química , Cumarinas/síntesis química , Naftoles/química , Naftoles/síntesis química , Acrilatos/química , Benzofuranos/química , Estereoisomerismo , Especificidad por SustratoAsunto(s)
Benzofuranos/síntesis química , Ftalimidas/síntesis química , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Benzoatos/química , Benzofuranos/clasificación , Benzofuranos/farmacología , Productos Biológicos/síntesis química , Productos Biológicos/química , Productos Biológicos/farmacología , Ciclización , Lactonas/química , Oxidación-Reducción , Ftalimidas/clasificación , Ftalimidas/farmacologíaRESUMEN
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).
RESUMEN
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.
Asunto(s)
Naftoquinonas/síntesis química , Vitamina K/análogos & derivados , Vitamina K/síntesis química , Acrilatos/química , Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/química , Técnicas Químicas Combinatorias , Estructura Molecular , Naftoquinonas/química , Estereoisomerismo , Vitamina K/químicaRESUMEN
[reaction: see text] Condensation of the phthalide sulfide with an ortho-quinone monoketal was employed as a key step in the first total synthesis of a derivative of (+/-)-PD 116740.
Asunto(s)
Benzo(a)Antracenos/síntesis química , Benzofuranos/química , Hidroxilación , Quinonas/química , Estereoisomerismo , Sulfuros/químicaRESUMEN
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.
Asunto(s)
Acrilatos/química , Benzazepinas/química , Benzazepinas/síntesis química , Técnicas de Química Sintética/métodos , Estereoisomerismo , Especificidad por SustratoRESUMEN
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.