Titanium Alkoxide-Based Regioselective Alkyne-Alkyne Reductive Coupling Mediated by In Situ Generated Arylamidate.

Titanium alkoxide-based alkyne-alkyne reductive coupling mediated by in situ generated arylamidate is described. A high level of regioselectivity is achieved in 37 examples, where (,)-dienes are exclusively formed. To the best of our knowledge, this study represents the first example of an apparent amide and carbamate directing effect in metal-mediated reductive coupling.

[4 + 2]-Cycloaddition and 1,4-Addition of ortho-Quinone Methides by a Chiral Crotyl Silane.

Anhydrous FeCl in the presence of 2,6-lutidine promotes the substrate-controlled enantioselective [4 + 2]-cycloaddition and crotylation reaction between an enantioenriched ( S, E)-crotyl silane and in situ generated ortho-quinone methides ( oQMs). The reaction produces both the chiral chroman and crotylation products in a ratio reflective of the electronic nature of the parent oQM with overall combined yields up to 96%. A ring-opening and elimination sequence was subsequently developed to provide direct access to the crotylation products, containing two contiguous tertiary carbon stereocenters, in good yields and enantioselectivities.

Embedded Spheroids as Models of the Cancer Microenvironment.

To more accurately study the complex mechanisms behind cancer invasion, progression, and response to treatment, researchers require models that replicate both the multicellular nature and 3D stromal environment present in an tumor. Multicellular aggregates (i.e.

Kava analogues as agents for treatment of periodontal diseases: Synthesis and initial biological evaluation.

Six kava analogues of the structural type 3-oxocyclohex-1-en-1-yl benzoates (and corresponding benzamides) were synthesized and evaluated for their affect on periodontal deconstruction in collagen anti-body primed oral gavage model of periodontitis. The compounds were prepared through an acylation or amidation of the enolizable cyclic 1,3-diketone. We have learned that three of the analogues are responsible for the reduction of inflammatory cell counts within soft tissue.

Mimicking the tumor microenvironment to regulate macrophage phenotype and assessing chemotherapeutic efficacy in embedded cancer cell/macrophage spheroid models.

Unlabelled: Tumor associated macrophages (TAMs) are critical stromal components intimately involved with the progression, invasion, and metastasis of cancer cells. To address the need for an in vitro system that mimics the clinical observations of TAM localizations and subsequent functional performance, a cancer cell/macrophage spheroid model is described. The central component of the model is a triple negative breast cancer spheroid embedded in a three-dimensional collagen gel.

Total Synthesis of Nuclear Factor of Activated T-Cells-68 (NFAT-68): Sequential Use of Chiral Allenylsilane and Titanium Alkoxide-Mediated Reductive Coupling Bond Construction.

Highly enantioenriched chiral allenylsilanes 4 were prepared in high yield through a scalable synthetic sequence, employing a modified copper-catalyzed SN2' reaction. These reagents were used for the production of enantioenriched homoproparglylic ethers 5, which were subjected to titanium alkoxide-mediated reductive coupling with acetylenic esters to produce (E,E)-dienes 6 bearing α,β,γ,δ-unsaturated esters. Both enantiomers of nuclear factor of activated T-cells-68 (NFAT-68) were synthesized in five steps with the sequential use of the two methods.

Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide.

Porphyromonas gingivalis (P.g.)-induced TNF-α can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner.

Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles.

Drug dose, high local target tissue concentration, and prolonged duration of exposure are essential criteria in achieving optimal drug performance. However, systemically delivered drugs often fail to effectively address these factors with only fractions of the injected dose reaching the target tissue. This is especially evident in the treatment of peritoneal cancers, including mesothelioma, ovarian, and pancreatic cancer, which regularly employ regimens of intravenous and/or intraperitoneal chemotherapy (e.

Total synthesis of (+)-isatisine a: application of a silicon-directed mukaiyama-type [3 + 2]-annulation.

Complete details of an asymmetric synthesis of (+)-isatisine A (1) are described. The synthesis highlights the use of a highly diastereoselective Mukaiyama-type [3 + 2]-annulation of allylsilane 5 with the unsaturated aldehyde 9a to assemble the functionalized tetrahydrofuran core of isatisine A. A convergent route to the framework of the natural product was established that employed a substrate-controlled indole coupling that was followed by a late-stage intramolecular copper(I)-mediated amidation to complete the assembly of the tetracyclic framework of (+)-isatisine A.

The chemistry and engineering of polymeric hydrogel adhesives for wound closure: a tutorial.

The closure and repair of wounds after traumatic or surgical injury is of significant clinical and research importance. While sutures remain the common wound closure technique, they have many disadvantages. Consequently, polymeric hydrogel adhesives have emerged as essential materials for wound management and repair because of their tunable chemical and physical properties, which enable them to adhere or stick to tissues, possess sufficient mechanical strength to stay intact and be subsequently removed, provide complete wound occlusion, and act as a barrier to bacterial infection.

Synthesis of isochromene-type scaffolds via single-flask Diels-Alder-[4 + 2]-annulation sequence of a silyl-substituted diene with menadione.

A sequential Diels-Alder reaction/silicon-directed [4 + 2]-annulation was developed to assemble hydroisochromene-type ring systems from menadione 2. In the first step, a Diels-Alder of the 1-silyl-substituted butadiene 1 with 2 furnished an intermediate cyclic allylsilane. Subsequently, TMSOTf promoted a [4 + 2]-annulation through trapping of an oxonium, generated by condensation between an aldehyde and the TBS protected alcohol resulted in the formation of a cis-fused hydroisochromene 13.

Bifunctional homoallylic carbamates from chiral silane additions to in situ generated N-acyl iminium ions.

Homoallylic carbamates bearing an α,β-unsaturated ester or an allylic carbonate were generated respectively utilizing novel chiral silanes through Lewis acid promoted asymmetric aminocrotylation. Those bifunctional building blocks could further undergo Michael addition or cyclization to selectively form functionalized lactams, azetidines, and tetrahydropyrimidinones.

From Brittle to Pliant Viscoelastic Materials with Solid State Linear Polyphosphonium - Carboxylate Assemblies.

A polystyrenylphosphonium polymer was synthesized and complexed with various carboxylic acid derivatives to form new solid-state polyelectrolyte-surfactant assemblies. The properties of these ionic materials were highly dependent on the nature of the anion and included a brittle material, a rubbery ball that bounces, or a sticky fiber. The values for the equilibrium modulus, storage modulus, and loss modulus were dependent on the composition of the carboxylic acid and the number of electrostatic interactions.

Total synthesis of (-)-virginiamycin M2: application of crotylsilanes accessed by enantioselective Rh(II) or Cu(I) promoted carbenoid Si-H insertion.

A stereoselective synthesis of the antibiotic (-)-virginiamycin M(2) is detailed. A convergent strategy was utilized that proceeded in 10 steps (longest linear sequence) from enantioenriched silane (S)-15. This reagent, which was prepared via a Rh(II)- or Cu(I)-catalyzed carbenoid Si-H insertion, was used to introduce the desired olefin geometry and stereocenters of the C1-C5 propionate subunit.

Total synthesis of (+)-SCH 351448.

A convergent synthesis of (+)-SCH 351448 (1), a monosodium salt of a C(2)-symmetric macrodiolide, is described. Our approach is based on a [4 + 2] annulation with a chiral allyl silane (anti-5c) to assemble the pyran subunits. Homodimerization was carried out in a stepwise fashion; initial esterification at C29' followed by macrocyclization at C29 afforded the desired macrodiolide.

Bioactive stent surface coating that promotes endothelialization while preventing platelet adhesion.

A bifunctional peptide coating was designed, synthesized, and evaluated as a potential pro-healing stent coating. The bifunctional peptide consisted of a short 28-mer sequence that on the N-terminus has a motif with affinity for polystyrene binding and at the C-terminus has a motif that was shown to bind selectively human endothelial cells but not platelets. Results showed that the selective coating, a polystyrene-binding peptide terminated in RRETAWA (FFSFFFPASAWGSSGSSGK(biotin)CRRETAWAC), bound endothelial cells quantitatively as well as the common RGD motif, but unlike RGD, it did not show any preference for platelet adherence.

Total synthesis of (+)-isatisine A.

Total synthesis of (+)-isatisine A is described based on the application of a silyl-directed Mukaiyama-type [3 + 2]-annulation for the preparation of a fully substituted furan core. The indole branch forming the quaternary carbon center at C2 was constructed by addition to an intermediate N-acyliminium ion derived from aminal 4. In addition, the fused tetracyclic framework including furan core was built up using modified Buchwald amidation conditions.

A versatile reagent to synthesize diverse ionic liquids ranging from small molecules and dendrimers to functionalized proteins.

An ionic liquid "reagent" bearing a succinimidyl activated ester is reported that can be used to synthesize a variety of small molecule and macromolecular ionic liquids. In addition, the ionic liquid reagent was used to modify lysozyme, and the protein retained its structure and function after modification. This study describes a facile and reliable route to new ionic liquid compositions.

Acidic polysaccharide mimics via ring-opening metathesis polymerization.

An efficient and general synthetic strategy for the preparation of high-molecular-weight hydrophilic polymers bearing both carboxylic acid and hydroxyl pendant groups is described. Specifically, poly(5,6-dihydroxyoxanorbornane carboxylic acid) with molecular weight ranging from ∼100 000 to 5 000 000 g/mol was prepared by ring-opening metathesis polymerization of methyl 5-oxanorbornene-2-carboxylate in the presence of Grubbs catalyst II and subsequently modified to tune the hydrophobic/hydrophilic properties by the introduction of either hydroxyl or carboxylic acid functionalities. These polymers mimic the natural acidic polysaccharide alginate and form hydrogels with polylysine.

Biomedical applications of dendrimers: a tutorial.

Since their development in the mid-80s, dendrimers have become prominent synthetic macromolecules in the field of biomedical science. This tutorial review begins by discussing pertinent background information about dendrimers, focusing on their behavior in solution, how they are synthesized and what advantages they have over linear polymers. Then the focus of the review shifts to the biomedical applications of dendrimers, including their use in drug delivery, tissue engineering, gene transfection, and contrast enhancement for magnetic resonance imaging.

Stereoselective C-glycosidations with achiral and enantioenriched allenylsilanes.

Allenylsilanes are used as carbon nucleophiles in highly stereoselective Lewis acid-promoted C-glycosidations, resulting in the introduction of an internal alkyne with an adjacent stereocenter. Both achiral and chiral allenylsilanes form the desired products with high diastereoselectivity, where the nucleophile adds exclusively to the α-face of the intermediate oxonium ion. Reactions with glucal and galactal afford dihydropyran products, while reactions with a ribose derivative yield dihydrofuran products.

Ease of synthesis, controllable sizes, and in vivo large-animal-lymph migration of polymeric nanoparticles.

Polymeric nanoparticles were synthesized using both a photoinduced and base-catalyzed free radical polymerization method. These mild room temperature approaches allow sensitive molecules, such as dyes, to be encapsulated. Using this method, near infrared dye loaded nanoparticles for lymphatic migration and lymph nodes localization were synthesized.

Synthesis of reblastatin, autolytimycin, and non-benzoquinone analogues: potent inhibitors of heat shock protein 90.

A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams.