RESUMEN
In this study, we propose heavy-metal-free reductive coupling of arylacetylenes with benzothiazole sulfones. The reactions of alkyl or benzylic benzothiazole sulfones with arylacetylenes are successfully performed in the presence of Hantzsch esters and K2CO3 under visible-light irradiation to afford 1,2-disubstituted alkenes in moderate to good yields, with Z-isomer as the major product. The utility of this protocol is expanded to α-deuterative coupling using a deuterated Hantzsch ester, furnishing the corresponding alkenes with high deuterium incorporation.
RESUMEN
New synthetic methods for spirolactams bearing an α-methylene-γ-butyrolactone or its analogous methylene-lactam have been developed. The allylation of γ-phenylthio-functionalized γ-lactams with 2-(acetoxy)methyl acrylamides was accomplished by using 2.5 equivalents of NaH to give the corresponding adducts in excellent yields. The remaining phenylthio group was substituted with a hydroxy group by treatment with CuBr, and the resulting γ-hydroxyamides were cyclized under acidic conditions to afford the corresponding methylene-lactam-fused spirolactams in high yields. On the other hand, methylene-lactone-fused spirolactams could be delivered from the allyl adducts in high yields through a sequential N-Boc protection/desulfinative lactonization.
RESUMEN
We have developed a new photon upconversion (UC) system utilizing a new amphiphilic sensitizer 1a that comprises a hydrophilic ruthenium complex and a lipophilic bisanthracene appendage. At concentrations higher than 5 µM in toluene, the sensitizer 1a formed a reverse micellar assembly which facilitated the triplet sensitization of 9,10-diphenylanthracene (DPA) more efficiently than homogeneously dispersed solutions to enhance the UC efficiency up to 38.2%. The Stern-Volmer analyses revealed the stepwise triplet-triplet energy transfers (TTET): (1) intramicellar energy transfer from the ruthenium core to the bisanthracene surface and (2) diffusion-dependent energy transfer from the surface to DPA. On these bases, it can be assumed that the reverse micellar assemblies accelerate the former TTET process to enhance the UC efficiency.
RESUMEN
Pharmaceutically attractive methylene lactone- and methylene lactam-based spiro compounds have been synthesized by employing amido-functionalized γ-hydroxylactam as a common intermediate. Development of a new route for bifurcated synthesis of two types of N,O-spiro compounds was accomplished by treatment of the intermediate under acidic conditions, leading to potent cytotoxic methylene lactone-based spiro compounds. New methylene lactam-based N,N-spiro compounds could be delivered via N-tert-butyloxycarbonyl protection of the terminal amide moiety of the intermediate followed by lactam cyclization under basic conditions.
Asunto(s)
Antineoplásicos/farmacología , Lactamas/farmacología , Lactonas/farmacología , Compuestos de Espiro/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Lactamas/química , Lactonas/química , Ratones , Modelos Moleculares , Estructura Molecular , Compuestos de Espiro/síntesis química , Compuestos de Espiro/químicaRESUMEN
The catalytic enantioselective propargylation of aldehydes with newly prepared stannyl allenyl amides is described. The reaction has been accomplished by using catalytic amounts of indium chloride, zinc chloride, and a chiral BINOL derivative, affording amide-functionalized homopropargyl alcohols in excellent yields and enantioselectivities.
RESUMEN
Practical synthesis of bay-monofunctionalized perylene dyes has been developed based on controllable NBS bromination of tetrabenzyl perylene-3,4,9,10-tetracarboxylate. The ability to perform the convenient and high-yielding synthesis highlights the potential utility of our multifunctional approach to access a diverse range of new perylene systems.
RESUMEN
A highly enantioselective amide allylation of α-iminoamides has been achieved using catalytic amounts of InCl3, ZnCl2 and a BINOL derivative. This reaction allowed facile access to a variety of amide functionalised α-methylene-γ-butyrolactams in excellent yields with high enantioselectivities.
Asunto(s)
Compuestos Alílicos/síntesis química , Amidas/química , Indio/química , Lactamas/síntesis química , Compuestos Alílicos/química , Catálisis , Lactamas/química , Estructura Molecular , EstereoisomerismoRESUMEN
This article is a full account of the work exploring the potential utility of catalytic enantioselective amide allylation of various isatins using indium-based chiral catalysts. A survey of various isatin substrates and NH-containing stannylated reagents revealed that the reaction has a remarkably wide scope to result in extremely high yields and enantioselectivities (up to >99 %, 99 %â ee) of variously substituted homoallylic alcohols. Several mechanistic investigations demonstrated that the substrate-reagent hydrogen-bond interaction plays a critical role in the formation of the key transition states to result in enhanced catalytic reaction. The success of this approach allowed convenient access to chiral 2-oxindoles spiro-fused to the α-methylene-γ-butyrolactone functionality and their halogenated derivatives in almost enantiopure forms, thus highlighting the general utility of this synthetic method to deliver a large variety of antineoplastic drug candidates and pharmaceutically meaningful compounds.
Asunto(s)
4-Butirolactona/análogos & derivados , Amidas/química , Indoles/química , Isatina/química , Compuestos de Espiro/química , 4-Butirolactona/química , Catálisis , Modelos Moleculares , Estructura Molecular , Oxindoles , EstereoisomerismoRESUMEN
This communication reports a significant breakthrough on the novel catalytic amide allylation to the acyclic α-ketoester systems, achieving satisfactorily high yields and extremely high levels of the asymmetric induction to allow for highly enantioselective synthesis of ester functionalised α-methylene-γ-butyrolactones.
Asunto(s)
4-Butirolactona/análogos & derivados , Amidas/química , 4-Butirolactona/síntesis química , 4-Butirolactona/química , Catálisis , Técnicas de Química Sintética , Ésteres , Estereoisomerismo , Especificidad por SustratoRESUMEN
For the efficient approach to medicinally important α-branched 3-acyltetramic acids, the key reaction of O- to C- acyl rearrangement using α-amino-acid-derived 4-O-acyltetramic acids was extensively examined in the presence of various metal salts. Use of CaCl(2) or NaI dramatically changed the results in the reaction efficiency and rapidly brought about the desired α-branched 3-acyltetramic acids in markedly improved yields. We also discuss an epimerization at C5 stereocenter under the rearrangement conditions as well as the tolerance for structural variation at C3 and C5. In addition to the preceding success in the total synthesis of new cytotoxic tetramic acid, penicillenol A(1), this methodology could be also applied to the first total synthesis of penicillenol A(2).
Asunto(s)
Aminoácidos/síntesis química , Pirrolidinonas/síntesis química , Aminoácidos/química , Estructura Molecular , Pirrolidinonas/química , EstereoisomerismoRESUMEN
A new synthetic approach to (+)-batzellaside B from naturally abundant L-pyroglutamic acid is presented in this article. The key synthetic step involves Sharpless asymmetric dihydroxylation of an olefinic substrate functionalized with an acetoxy group to introduce two chiral centres diastereoselectively into the structure. Heterocyclic hemiaminal 4, which could be converted from the resulting product, was found to provide stereospecific access to enantiomerically enriched allylated intermediate, offering better prospects for the total synthesis of this natural product.
RESUMEN
A visible-light-induced desulfonylative Giese-type reaction has been developed. Essential to the success is the employment of Hantzsch ester to activate benzothiazole sulfones without any heavy-metal additives. Not only benzylic benzothiazole sulfones but also alkyl ones were viable substrates and reacted with electron-deficient alkenes and a propiol amide.
RESUMEN
A novel and facile synthesis of azaspiro-γ-lactones with a methylene-lactam framework from N-carbonyl imides is described. Mechanistic investigations provide evidence for a two-step reaction process involving ZnCl(2)-promoted addition of ß-amido allylindium species followed by an unexpectedly molecular-sieves-mediated ring opening-reclosure concomitantly with the loss of an N-carbonyl unit.
Asunto(s)
Amidas/química , Compuestos Aza/síntesis química , Imidas/química , Indio/química , Lactamas/química , Lactonas/síntesis química , Compuestos de Espiro/síntesis química , Compuestos Aza/química , Catálisis , Cloruros/química , Lactonas/química , Estructura Molecular , Compuestos de Espiro/química , Compuestos de Zinc/químicaRESUMEN
A simple and straightforward synthetic approach was developed to access a biologically important class of alpha-aminomethyl-gamma-butyrolactones via a beta-lactam synthon strategy involving successive ring-opening and lactonization processes from alpha-hydroxyethyl-substituted beta-lactams that were elaborated by SmI2-mediated reductive coupling reaction.
Asunto(s)
Lactonas/síntesis química , beta-Lactamas/química , 4-Butirolactona/análogos & derivados , Yoduros/farmacología , Lactonas/química , Espectroscopía de Resonancia Magnética , Oxidación-Reducción , Samario/farmacologíaRESUMEN
Batzellasides A-C are C-alkylated piperidine iminosugars isolated from a sponge, Batzella sp. The first total synthesis of (+)-batzellaside B was achieved by employing a chiral pool approach starting from L-arabinose for the construction of a piperidine ring system. Subsequently, a practical second-generation synthesis was developed by utilizing a Sharpless asymmetric dihydroxylation for the preparation of the common piperidine intermediate elaborated in the first-generation synthesis. The overall yield of batzellaside B was improved to 3.3% by introducing the exocyclic C8 stereocenter via facial selective hydride addition to a linear ketone. These syntheses allowed for the determination of the absolute stereochemistry of this natural product as well as for providing precious samples, which would pave the way for further biological studies.
Asunto(s)
Amino Azúcares/síntesis química , Amino Azúcares/química , Modelos Moleculares , Conformación MolecularRESUMEN
A remarkably effective method allowing an extremely high enantioselective synthesis of the spiro-fused 2-oxindole/α-methylene-γ-butyrolactones is described. The key strategy lies in the use of indium-catalyzed asymmetric amide allylation of N-methyl isatin with functionalized allylstannanes, which can lead to the antineoplastic spirocyclic lactones in almost enantiopure forms.
Asunto(s)
4-Butirolactona/análogos & derivados , Amidas/química , Indoles/síntesis química , Isatina/química , Compuestos Organometálicos/química , Compuestos de Espiro/síntesis química , 4-Butirolactona/síntesis química , 4-Butirolactona/química , Catálisis , Indio/química , Indoles/química , Estructura Molecular , Oxindoles , Compuestos de Espiro/química , EstereoisomerismoRESUMEN
The first total synthesis of antibacterial epicoccarine A isolated from a fungus Epicoccum sp. has been accomplished in 10 steps along with synthetic elaboration of its C5-epimer, highlighting the utility of O- to C-acyl rearrangement of a 4-O-acyltetramic acid derivative. Comparison of spectroscopic properties and specific optical rotations of the synthetic samples with those reported for authentic material has clearly indicated the unspecified absolute stereochemistry of this natural product to be 5S.
Asunto(s)
Pirrolidinonas/síntesis química , Estructura Molecular , EstereoisomerismoRESUMEN
Detailed exploratory and mechanistic investigations on spontaneous formation of dye-functionalized gold nanoparticles (GNPs) using dye-based reverse micellar systems are described in this publication. The accumulated results from spectroscopic and microscopic investigations demonstrated that water molecules confined within nanoscopic enclosure of the self-assembled reverse micelles played critical role in the redox processes of aurate ions to produce GNPs, which are assumed to have approximately constant size distributions. The resulting dye-functionalized GNPs were found to offer their absorption and fluorescence emission tunability by changing the medium polarity as well as to exhibit excellent film-forming properties to give optically homogeneous polystyrene thin films. These key findings in addition to broad applicability of the self-assembling process with a variety of dye analogues have led to a conclusion that the protocol presented here serves as a versatile synthetic method to provide a potential convenience for future development of new organic-inorganic hybrid nanomaterials.
RESUMEN
We have developed a direct, asymmetric Michael reaction that can be performed in brine or seawater without addition of organic solvents. A bifunctional catalyst with long hydrophobic alkyl chains efficiently catalyzed Michael reactions and afforded the desired products in excellent yield with high enantiomeric excess, even when only an equal molar ratio of the donor to acceptor was used.
RESUMEN
We have developed direct asymmetric cross-aldol reactions that can be performed in water without addition of organic solvents. A bifunctional catalyst with a long hydrophobic alkyl chain efficiently catalyzed the reactions and afforded the desired aldol products in excellent yield with high enantiomeric excess, even when only an equal molar ratio of the donor and acceptor was used. These results reveal an effective design strategy for the development of aqueous organocatalytic systems.