Search results for "combinatorial"

Black-Box solvers in combinatorial optimization

2015

Black box optimizers have a long tradition in the field of operations research. These procedures treat the objective function evaluation as a black box and therefore do not take advantage of its specific structure. Black-box optimization refers to the process in which there is a complete separation between the evaluation of the objective function —and perhaps other functions used to enforce constraints— and the solution procedure. The challenge of optimizing black boxes is to develop methods that can produce outcomes of reasonable quality without taking advantage of problem structure and employing a computational effort that is adequate for the context.

Synthesis and Topological Determination of Hexakis-Substituted 1,4-Ditritylbenzene and Nonakis-Substituted 1,3,5-Tritritylbenzene Derivatives: Buildi…

2012

Based on trityl moieties, novel organic building blocks have been prepared and structurally investigated. Substituted hexaphenyl-p-xylene (1,4-ditritylbenzene) as well as extended analogues thereof were prepared. Furthermore, a new family based on a 1,3,5-tritritylbenzene motif, connecting three trityl groups through a formal mesitylene unit, was developed. Both families were further converted through six- and nine-fold substitution reactions, respectively, to yield potent molecular building blocks for supramolecular assemblies.

Frontispiece: Fluorine‐Containing Drugs Approved by the FDA in 2018

2019

Hydrogels for potential colon drug release by thiol-ene conjugate addition of a new inulin derivative.

2008

Inulin was chosen as a starting polymer for biocompatible, pH-sensitive and biodegradable hydrogels. Three INUDVSA-TT hydrogels were obtained by crosslinking inulin derivatives with trimethylolpropane tris(3-mercaptopropionate) under varying conditions. The resulting hydrogels were cell compatible, as demonstrated by MTS and trypan blue exclusion assays acting on Caco-2 cells, and were biodegraded by inulinase and esterase, thus suggesting their use as colonic drug delivery systems. 2-Methoxyestradiol, an anti-cancer drug, was soaked in INUDVSA-TT hydrogels and its in vitro release and apoptotic effect on Caco-2 cells were evaluated.

Polyoxometalate Metal–Organic Frameworks: Keggin Clusters Encapsulated into Silver-Triazole Nanocages and Open Frameworks with Supercapacitor Perform…

2019

To investigate the relationship between the structures of polyoxometalate host–guest materials and their energy-storage performance, three novel polyoxometalate-based metal–organic compounds, [Ag10...

Amphiphilic Polyphenylene Dendron Conjugates for Surface Remodeling of Adenovirus 5

2020

Abstract Amphiphilic surface groups play an important role in many biological processes. The synthesis of amphiphilic polyphenylene dendrimer branches (dendrons), providing alternating hydrophilic and lipophilic surface groups and one reactive ethynyl group at the core is reported. The amphiphilic surface groups serve as biorecognition units that bind to the surface of adenovirus 5 (Ad5), which is a common vector in gene therapy. The Ad5/dendron complexes showed high gene transduction efficiencies in coxsackie‐adenovirus receptor (CAR)‐negative cells. Moreover, the dendrons offer incorporation of new functions at the dendron core by in situ post‐modifications, even when bound to the Ad5 sur…

Towards a fully synthetic MUC1-based anticancer vaccine: efficient conjugation of glycopeptides with mono-, di-, and tetravalent lipopeptides using c…

2011

Abstract The membrane-bound tumor-associated glycoprotein MUC1 is aberrantly glycosylated in cancer cells compared with normal cells, and is therefore considered an attractive target for cancer immunotherapy. However, tumor-associated glycopeptides from MUC1 do not elicit a sufficiently robust immune response. Therefore, antitumor vaccines were developed, which consist of MUC1 glycopeptides as the B epitopes and immune-stimulating toll-like receptor 2 (TLR 2) lipopeptide ligands. These fully synthetic vaccine candidates were prepared by solid-phase synthesis of the MUC1 glycopeptides. The Pam(3) Cys lipopeptide, also synthesized on solid-phase, was C-terminally coupled to oligovalent lysine…

Enantioselective Synthesis of Pyrrolizidinone Scaffolds through Multiple-Relay Catalysis

2020

A triple-tandem protocol for the synthesis of the pyrrolizidinone skeleton has been devised. It involves a cross metathesis-intramolecular aza-Michael reaction-intramolecular Michael addition tandem sequence, starting from N-pentenyl-4-oxo-2-alkenamides and conjugated ketones. In the presence of two cooperative catalysts, namely the second-generation Hoveyda-Grubbs catalyst and (R)-TRIP-derived BINOL phosphoric acid, this multiple-relay catalytic process takes place in good yields and outstanding levels of diastero- and enantioselectivity with the simultaneous generation of three contiguous stereocenters.

Asymmetric tandem reactions: New synthetic strategies

2010

The use of domino and multicomponent reactions in asymmetric synthesis is constantly increasing nowadays. This allows for the synthesis of complex molecules in a single synthetic sequence, usually with high atom economy. Herein, we report three examples of new asymmetric tandem reactions recently developed in our laboratories, giving rise to new families of enantiomerically enriched fluorinated and nonfluorinated heterocycles. Thus, 1,4-dihydropyridines (1,4-DHPs) bearing fluorinated substituents at C6 were assembled by means of a Hantzsch-type reaction; cyclic β-amino carbonyl derivatives were prepared using a cross-metathesis (CM)–intramolecular aza-Michael sequence; while fluorinated ind…

ChemInform Abstract: Microwave-Assisted Tandem Cross Metathesis Intramolecular Aza-Michael Reaction: An Easy Entry to Cyclic β-Amino Carbonyl Derivat…

2008

Hoveyda−Grubbs catalyst in combination with BF3·OEt2 efficiently promotes tandem cross metathesis intramolecular aza-Michael reaction between enones and unsaturated carbamates resulting in the creation of β-amino carbonyl units. The use of microwave irradiation dramatically accelerates the process, enhancing the synthetic utility of this methodology for the preparation of these types of derivatives. When enantiomerically enriched α-branched amines were used as starting materials, the process was also very efficient, although with modest selectivity in the newly created stereocenter. The use of microwave irradiation led to an interesting effect, inverting the selectivity in the addition proc…