RESUMO
Herein we report the N-heterocyclic carbene (NHC)-catalyzed [3 + 2] annulation of α,ß-unsaturated aldehydes with carbamoylpropiolates via an unusual enolate pathway leading to the construction of highly functionalized maleimides or isomaleimides. The electronic effect imposed by the alkyl/aryl group present on the amide nitrogen of carbamoylpropiolates plays a crucial role in the selective formation of these important five-membered heterocyclic building blocks. The developed protocol is mild and tolerates a wide range of substituents on both substrates. The application of this protocol in the synthesis of the antibacterial natural product Aspergillus FH-X-213 has also been demonstrated.
Assuntos
Aspergillus , Catálise , Maleimidas , Metano/análogos & derivados , EstereoisomerismoRESUMO
Lewis base-catalyzed allylic alkylation of Morita-Baylis-Hillman adducts with α-SCF3 ketones has been demonstrated. The developed strategy provides efficient access to a series of highly functionalized scaffolds featuring trifluoromethanesufinyl motif on a stereogenic carbon.
RESUMO
Ru-catalyzed regioselective cascade annulation of acrylamides with 2-alkynoates via aza-Michael/C-H activation sequence for the synthesis of various 6-oxo nicotinic acid esters is described. The regioselectivity of the protocol has been confirmed by performing silver mediated protodecarboxylation of the corresponding 6-oxo nicotinic acid to furnish 2-pyridone. The developed protocol is copper or silver salt-free and uses inexpensive, safe, and environmentally benign peroxide-based "oxone" as the sole oxidant. A redox-neutral version of the protocol is also demonstrated.
RESUMO
A novel, efficient, and regioselective transition-metal-free one-pot synthesis of aryl sulfones via the reactive quinone imine ketal intermediate is demonstrated using easily accessible bench-stable sulfinate salts. A broad range of functionality on p-anisidine substrates as well as sulfinate salts was tolerated under mild reaction conditions to provide the corresponding aryl sulfones in good to excellent yields.
RESUMO
Chiral N-heterocyclic carbene (NHC)-catalyzed intramolecular [3 + 2] annulation of enals with an unactivated imine moiety of quinazolinone via formal homoenolate cycloaddition has been demonstrated. It is an excellent approach for stereoselective syntheses of deoxy-cruciferane alkaloids comprising a biologically important pyrroloindoline scaffold. Notably, this is the first report on the NHC-catalyzed asymmetric intramolecular homoenolate annulation with cyclic N-acyl amidine.
RESUMO
Ruthenium-catalyzed amide directed Csp2-H activation of the quinazolinone scaffold has been demonstrated, leading to the selective mono- or dialkenylation in moderate to good yields to achieve medicinally important stilbene containing quinazolinones. The terminal alkyne is utilized as a coupling partner, which resulted in the selective trans-alkene formation. Electron-deficient phenylacetylenes facilitate alkenylation followed by tandem hydroamidation of the newly generated trans-double bond to provide novel quinazolinone alkaloids related to the Luotonine class of natural products.
RESUMO
A concise synthesis of functionalized cyclohexenone-fused spirobenzofuran-3-ones under mild reaction conditions was developed. The reaction proceeds via insertion of aryne into the C-O bond followed by a regioselective intramolecular conjugate addition. The use of silyl-protected acid was crucial for the transformation. This protocol was successfully applied for the synthesis of leptosphaerin C core and its novel analogues.
RESUMO
The quinazolinone ring has been exploited as a directing group for C(sp3)-H functionalization for the first time. The proximal C-γ(sp3)-H bonds have been oxidized by palladium-catalyzed acetoxylation reaction. Various functional groups on the quinazolinone scaffold were tolerated to provide novel quinazolinone derivatives. The use of base was found to be crucial for the monoselective acetoxylations.
RESUMO
The Pd-catalyzed quinazolinone-directed regioselective monoarylation of aromatic rings by C-H bond activation is developed. A broad substrate scope is demonstrated for both quinazolinone as well as diaryliodonium triflates. The use of a base was found to be crucial for this transformation, unlike for the known nitrogen-directed arylations. All of the novel quinazolinones of biological interest were synthesized by using the operationally simple Pd(II)-catalyzed arylation reaction.
RESUMO
A new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based probe molecule (L) is synthesized for specific binding to Hg2+ ion in physiological condition with an associated luminescence ON response in the near-IR region of the spectrum. Appropriate functionalization in the 5-position of each of two pyrrole moieties with styryl functionality in a BODIPY core helped us in achieving the extended conjugation and a facile intramolecular charge transfer transition with a narrow energy gap for frontier orbitals. This accounted for a poor emission quantum yield for the probe molecule L. Binding to Hg2+ helped in interrupting the facile intramolecular charge transfer (ICT) process that was initially operational for L. This resulted in a hypsochromic shift of absorption band and a turn-on luminescence response with λMaxEms of 650 nm on specific binding to Hg2+. Observed spectral changes are rationalized based on quantum chemical calculations. Interestingly, this reagent is found to be localized preferentially in the mitochondria of the live human colon cancer (Hct116) cells. Mitochondria is one of the major targets for localization of Hg2+, which actually decreases the mitochondrial membrane potential and modifies various proteins having sulfudryl functionality(ies) to cause cell apoptosis. Considering these, ability of the present reagent to specifically recognize Hg2+ in the mitochondrial region of the live Hct116 cells has significance.
Assuntos
Mercúrio/metabolismo , Mitocôndrias/metabolismo , Sondas Moleculares , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Água/química , Células HCT116 , HumanosRESUMO
The total and semi-synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium Sorangium cellulosum, are reported. The thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards Mycobacterium tuberculosis. This study focuses on 1)â thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacinsâ A-C, 2)â the roles of the thiazole ring, and 3)â the hexyl side chain at C2. Semi-synthetic O-methylation at C17 suppressed the transacylations without a substantial loss of antibacterial activity. Exchanging the C17-C25 side chain for simplified hydrophobic chains led to complete loss of antibacterial activity. Exchange of the thiazole by an oxazole ring or removal of the hexyl side chain at C2 had no substantial effect on the biological properties.
Assuntos
Antibacterianos/química , Macrolídeos/química , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Ammonium persulfate-dimethyl sulfoxide (APS-DMSO) has been developed as an efficient and new dehydrating reagent for a convenient one-pot process for the synthesis of miscellaneous cyclic imides in high yields starting from readily available primary amines and cyclic anhydrides. A plausible radical mechanism involving DMSO has been proposed. The application of this facile one-pot imide forming process has been demonstrated for a practical synthesis of vernakalant.
RESUMO
The direct regioselective allylation of inâ situ generated aldehyde acyl anions has been achieved by synergistic NHC and Pd catalysis. It provides an efficient access to valuable ß,γ-unsaturated ketones under mild reaction conditions starting from easily accessible allylic carbonates and aldehydes without any preactivation. The synergistic catalysis method demonstrated herein adds a new dimension to the area of metal-mediated Câ allylation.
RESUMO
The direct visible light-mediated intramolecular decarboxylative C-H functionalization of Csp2 -H bond adjacent to the nitrogen of a heteroarene has been achieved by iridium-catalyzed photodecarboxylative radical cyclization. This method offers rapid entry to the synthesis of quinazolinone scaffolds from easily accessible starting materials. The newly developed protocol is mild, operationally simple, oxidant free and general. The utility of this unique Csp3 -Csp2 bond forming reaction has been demonstrated in the syntheses of Circumdatin, Sclerotigenine and Benzomalvin A class of quinazolinone natural products and their congeners. The present work represents an interesting example of use of memory of chirality in decarboxylative C-C bond forming enantioselective photoredox reaction.
RESUMO
Traditionally, toxic and expensive hydrazine building blocks are required to construct pharmaceutically important pyrazolidine-3,5-diones. Herein, we have described a novel method for their synthesis based on metal-free oxidative dehydrogenative N-N bond formation by PIDA-mediated reaction of easily accessible dianilide precursors. The developed mild reaction protocol features a good functional group tolerance and scalability. The application of this method is demonstrated by offering a unique route for the synthesis of uricosuric agents G-25671 and sulfinpyrazone from inexpensive starting material aniline via smooth functionalization of the well-designed diversity-oriented cyclopropyl key intermediate.
Assuntos
Sulfimpirazona , Uricosúricos , OxirreduçãoRESUMO
A one-pot cascade approach for the synthesis of N-substituted indoles from amino alcohols and alcohols under additive and base-free conditions with the liberation of water as the only stoichiometric byproduct is reported. The commercially available bench-stable Ni(OTf)2 salt in combination with 1,2-bis(dicyclohexylphosphino)ethane (dcype) is very effective for this unprecedented catalytic transformation. A broad range of substrates including aromatic and aliphatic primary alcohols, cyclic and acyclic secondary alcohols, and various substituted 2-aminophenyl ethyl alcohols are employed in the reaction conditions to provide a diverse range of N-alkylated indoles. Mechanistic studies revealed that the reaction proceeds through tandem N-alkylation via hydrogen autotransfer followed by the cyclization of N-alkylated alcohol intermediate.
RESUMO
Copper-catalyzed amidation/dimerization of anilides via regioselective C(sp2)-H functionalization is achieved. The para-selective amidation is accomplished on the anilide aromatic ring via a radical pathway leading to C-N bond formation in the presence of ammonium persulfate as a radical source/oxidant for the copper catalyst. The developed protocol tolerates a wide range of anilide substrates. The regioselectivity is confirmed by single-crystal X-ray studies.
RESUMO
Controlled and efficient activation is the crucial aspect of designing an effective prodrug. Herein we demonstrate a proof of concept for a light activatable prodrug with desired organelle specificity. Mertansine, a benzoansamacrolide, is an efficient microtubule-targeting compound that binds at or near the vinblastine-binding site in the mitochondrial region to induce mitotic arrest and cell death through apoptosis. Despite its efficacy even in the nanomolar level, this has failed in stage 2 of human clinical trials owing to the lack of drug specificity and the deleterious systemic toxicity. To get around this problem, a recent trend is to develop an antibody-conjugatable maytansinoid with improved tumor/organelle-specificity and lesser systematic toxicity. Endogenous CO is recognized as a regulator of cellular function and for its obligatory role in cell apoptosis. CO blocks the proliferation of cancer cells and effector T cells, and the primary target is reported to be the mitochondria. We report herein a new mitochondria-specific prodrug conjugate (Pro-DC) that undergoes a photocleavage reaction on irradiation with a 400 nm source (1.0 mW cm-2) to induce a simultaneous release of the therapeutic components mertansine and CO along with a BODIPY derivative (BODIPY(PPH3)2) as a luminescent marker in the mitochondrial matrix. The efficacy of the process is demonstrated using MCF-7 cells and could effectively be visualized by probing the intracellular luminescence of BODIPY(PPH3)2. This provides a proof-of-concept for designing a prodrug for image-guided combination therapy for mainstream treatment of cancer.
RESUMO
Bile acid-polyaminocarboxylate conjugates containing NE3TA, a potential iron chelator displayed significant cytotoxicities in both HeLa and HT29 colon cancer cells, and cholic acid-NE3TA attached to an organic fluorophore was shown to enter the HT29 cancer cells.