The Experts below are selected from a list of 2931 Experts worldwide ranked by ideXlab platform
Daniel Romo - One of the best experts on this subject based on the ideXlab platform.
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bioinspired total synthesis and human proteasome inhibitory activity of salinosporAmide a homosalinosporAmide a and derivatives obtained via organonucleophile promoted bis cyclizations
Journal of Organic Chemistry, 2011Co-Authors: Henry Nguyen, Tatiana Gladysheva, Trisha Fremgen, Daniel RomoAbstract:A full account of concise, enantioselective syntheses of the anticancer agent (−)-salinosporAmide A and derivatives, including (−)-homosalinosporAmide, that was inspired by biosynthetic considerations is described. The brevity of the synthetic strategy stems from a key bis-cyclization of a β-keto Tertiary Amide, which retains optical purity enabled by A1,3-strain rendering slow epimerization relative to the rate of bis-cyclization. Optimization studies of the key bis-cyclization, enabled through byproduct isolation and characterization, are described that ultimately allowed for a gram scale synthesis of a versatile bicyclic core structure with a high degree of stereoretention. An optimized procedure for zincate generation by the method of Knochel, generally useful for the synthesis of salino A derivatives, led to dramatic improvements in side-chain attachment and a novel diastereomer of salino A. The versatility of the described strategy is demonstrated by the synthesis of designed derivatives including (...
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a 1 3 strain enabled retention of chirality during bis cyclization of β ketoAmides total synthesis of salinosporAmide a and homosalinosporAmide a
ChemInform, 2010Co-Authors: Henry Nguyen, Daniel RomoAbstract:(-)-SalinosporAmide A (IVa) and (-)-homosalinosporAmide A (IVb) are prepared via a diastereoselective bis-cyclization of β-keto Tertiary Amide of type (II) as key step.
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a1 3 strain enabled retention of chirality during bis cyclization of β ketoAmides total synthesis of salinosporAmide a and homosalinosporAmide a
Chemical Communications, 2010Co-Authors: Henry Nguyen, Daniel RomoAbstract:A concise, enantioselective synthesis of the Phase I anticancer agent, (−)-salinosporAmide A, is described. The brevity of the described strategy stems from a key bis-cyclization of a β-keto Tertiary Amide, accomplished on gram scale, which retains optical purity enabled by A1,3-strain rendering epimerization slow relative to the rate of bis-cyclization. The versatility of the strategy for derivative synthesis is demonstrated by the synthesis of (−)-homosalinosporAmide A.
Henry Nguyen - One of the best experts on this subject based on the ideXlab platform.
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bioinspired total synthesis and human proteasome inhibitory activity of salinosporAmide a homosalinosporAmide a and derivatives obtained via organonucleophile promoted bis cyclizations
Journal of Organic Chemistry, 2011Co-Authors: Henry Nguyen, Tatiana Gladysheva, Trisha Fremgen, Daniel RomoAbstract:A full account of concise, enantioselective syntheses of the anticancer agent (−)-salinosporAmide A and derivatives, including (−)-homosalinosporAmide, that was inspired by biosynthetic considerations is described. The brevity of the synthetic strategy stems from a key bis-cyclization of a β-keto Tertiary Amide, which retains optical purity enabled by A1,3-strain rendering slow epimerization relative to the rate of bis-cyclization. Optimization studies of the key bis-cyclization, enabled through byproduct isolation and characterization, are described that ultimately allowed for a gram scale synthesis of a versatile bicyclic core structure with a high degree of stereoretention. An optimized procedure for zincate generation by the method of Knochel, generally useful for the synthesis of salino A derivatives, led to dramatic improvements in side-chain attachment and a novel diastereomer of salino A. The versatility of the described strategy is demonstrated by the synthesis of designed derivatives including (...
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a 1 3 strain enabled retention of chirality during bis cyclization of β ketoAmides total synthesis of salinosporAmide a and homosalinosporAmide a
ChemInform, 2010Co-Authors: Henry Nguyen, Daniel RomoAbstract:(-)-SalinosporAmide A (IVa) and (-)-homosalinosporAmide A (IVb) are prepared via a diastereoselective bis-cyclization of β-keto Tertiary Amide of type (II) as key step.
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a1 3 strain enabled retention of chirality during bis cyclization of β ketoAmides total synthesis of salinosporAmide a and homosalinosporAmide a
Chemical Communications, 2010Co-Authors: Henry Nguyen, Daniel RomoAbstract:A concise, enantioselective synthesis of the Phase I anticancer agent, (−)-salinosporAmide A, is described. The brevity of the described strategy stems from a key bis-cyclization of a β-keto Tertiary Amide, accomplished on gram scale, which retains optical purity enabled by A1,3-strain rendering epimerization slow relative to the rate of bis-cyclization. The versatility of the strategy for derivative synthesis is demonstrated by the synthesis of (−)-homosalinosporAmide A.
Zhengchun Peng - One of the best experts on this subject based on the ideXlab platform.
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pH-Responsive Dual Drug-Loaded Nanocarriers Based on Poly (2-Ethyl-2-Oxazoline) Modified Black Phosphorus Nanosheets for Cancer Chemo/Photothermal Therapy
'Frontiers Media SA', 2019Co-Authors: Nansha Gao, Chenyang Xing, Haifei Wang, Liwen Feng, Xiaowei Zeng, Lin Mei, Zhengchun PengAbstract:Synergistic cancer therapy, such as those combining chemotherapeutic and photothermal methods, has stronger treatment effect than that of individual ones. However, it is challenging to efficiently deliver nanocarriers into tumor cells to elevate intracellular drug concentration. Herein, we developed an effective pH-responsive and dual drug co-delivery platform for combined chemo/photothermal therapy. An anticancer drug doxorubicin (DOX) was first loaded onto the surface of black phosphorus (BP). With poly(2-ethyl-2-oxazoline) (PEOz) ligand conjugated onto the polydopamine (PDA) coated BP nanosheets, targeted long circulation and cellular uptake in vivo was significantly improved. With another anticancer drug bortezomib (BTZ) loaded onto the surface of the nanocapsule, the platform can co-deliver two different drugs. The surface charge of the nanocapsule was reversed from negative to positive at the tumor extracellular pH (∼6.8), ionizing the Tertiary Amide groups along the PEOz chain, thus facilitating the cell internalization of the nanocarrier. The cytotoxicity therapeutic effect of this nanoplatform was further augmented under near-infrared laser irradiation. As such, our DOX-loaded BP@PDA-PEOz-BTZ platform is very promising to synergistic cancer therapy
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Data_Sheet_1_pH-Responsive Dual Drug-Loaded Nanocarriers Based on Poly (2-Ethyl-2-Oxazoline) Modified Black Phosphorus Nanosheets for Cancer Chemo/Photothermal Therapy.docx
2019Co-Authors: Nansha Gao, Chenyang Xing, Haifei Wang, Liwen Feng, Xiaowei Zeng, Lin Mei, Zhengchun PengAbstract:Synergistic cancer therapy, such as those combining chemotherapeutic and photothermal methods, has stronger treatment effect than that of individual ones. However, it is challenging to efficiently deliver nanocarriers into tumor cells to elevate intracellular drug concentration. Herein, we developed an effective pH-responsive and dual drug co-delivery platform for combined chemo/photothermal therapy. An anticancer drug doxorubicin (DOX) was first loaded onto the surface of black phosphorus (BP). With poly(2-ethyl-2-oxazoline) (PEOz) ligand conjugated onto the polydopamine (PDA) coated BP nanosheets, targeted long circulation and cellular uptake in vivo was significantly improved. With another anticancer drug bortezomib (BTZ) loaded onto the surface of the nanocapsule, the platform can co-deliver two different drugs. The surface charge of the nanocapsule was reversed from negative to positive at the tumor extracellular pH (∼6.8), ionizing the Tertiary Amide groups along the PEOz chain, thus facilitating the cell internalization of the nanocarrier. The cytotoxicity therapeutic effect of this nanoplatform was further augmented under near-infrared laser irradiation. As such, our DOX-loaded BP@PDA-PEOz-BTZ platform is very promising to synergistic cancer therapy.
James F Wolfe - One of the best experts on this subject based on the ideXlab platform.
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synthesis of succinimido 3 4 b indane and 1 2 3 4 5 6 hexahydro 1 5 methano 3 benzazocine 2 4 dione by sequential alkylation and intramolecular arylation of enolates derived from n n n n tetramethylbutanediAmides and n n n n tetramethylpentanediAmide
Journal of Organic Chemistry, 1999Co-Authors: Sushama A Dandekar, Stacey N Greenwood, Thomas D Greenwood, Stephane Mabic, Joseph S Merola, James M Tanko, James F WolfeAbstract:The tricyclic title compounds, 4 and 5, were synthesized by initial alkylation of the lithium monoenolates of N,N,N‘,N‘-tetramethylbutanediAmide (6) and N,N,N‘,N‘-tetramethylpentanediAmide (19) with 2-iodobenzyl chloride in liquid NH3 at −60 °C to afford 2-(2-iodobenzyl)-N,N,N‘,N‘-tetramethylbutanediAmide (9) and 2-(2-iodobenzyl)-N,N,N‘,N‘-tetramethylpentanediAmide (20) in yields of 88 and 87%, respectively. Treatment of 9 with KNH2 in liquid NH3 resulted in formation and intramolecular arylation of the less-substituted α-enolate to produce trans-1,2-bis(N,N-dimethylcarboxamido)indane (10a) in 60% yield. Selective hydrolysis of 10a with aqueous Na2O2 gave trans-1-(N,N-dimethylcarboxamido)indane-2-carboxylic acid (17), which was then converted to bridged succinimide 4 by transformation to trans-1-(N,N-dimethylcarboxamido)indane-2-carboxAmide (10c) followed by cyclization of this mixed primary/Tertiary Amide by means of NaH in refluxing THF. Treatment of 20 with KNH2 in liquid NH3 led to intramolecular aryl...
Giovanni F. Caramori - One of the best experts on this subject based on the ideXlab platform.
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Platinum-triggered Bond-cleavage of Pentynoyl Amide and N-propargyl handles for Drug-Activation
Journal of the American Chemical Society, 2020Co-Authors: Bruno Oliveira, Felipe S. S. Schneider, Benjamin Stenton, João Conde, Magda Negrão, Vb Unnikrishnan, Cátia Rebelo De Almeida, Carlos Cordeiro, Miguel Godinho Ferreira, Giovanni F. CaramoriAbstract:The ability to create ways to control drug activation at specific tissues while sparing healthy tissues remains a major challenge. The administration of exogenous target-specific triggers offers the potential for traceless release of active drugs on tumor sites from antibody−drug conjugates (ADCs) and caged prodrugs. We have developed a metal-mediated bond-cleavage reaction that uses platinum complexes [K 2 PtCl 4 or Cisplatin (CisPt)] for drug activation. Key to the success of the reaction is a water-promoted activation process that triggers the reactivity of the platinum complexes. Under these conditions, the decaging of pentynoyl Tertiary Amides and N-propargyls occurs rapidly in aqueous systems. In cells, the protected analogues of cytotoxic drugs 5fluorouracil (5-FU) and monomethyl auristatin E (MMAE) are partially activated by nontoxic amounts of platinum salts. Additionally, a noninternalizing ADC built with a pentynoyl traceless linker that features a Tertiary Amide protected MMAE was also decaged in the presence of platinum salts for extracellular drug release in cancer cells. Finally, CisPt-mediated prodrug activation of a propargyl derivative of 5-FU was shown in a colorectal zebrafish xenograft model that led to significant reductions in tumor size. Overall, our results reveal a new metal-based cleavable reaction that expands the application of platinum complexes beyond those in catalysis and cancer therapy.