The Effect of Capsaicin Derivatives on Tight-Junction Integrity and Permeability of Madin-Darby Canine Kidney Cells

Capsaicin is known to interfere with tight junctions (TJs) of epithelial cells and therefore to enhance paracellular permeability of poorly absorbable drugs. However, due to its low water solubility, pungency, and cytotoxicity, its pharmacologic use is limited. In this study, we investigated the effect of capsaicin derivatives of synthetic (e.g., 10-hydroxy-N-(4-hydroxy-3-methoxybenzyl)decanamide, etc.) and natural (olvanil and dihydrocapsaicin) origin on Madin-Darby Canine Kidney–C7 cells. Impedance spectroscopy was used to determine the transepithelial electrical resistance and the capacitance. Permeability assays with fluorescein isothiocyanate–dextran were carried out to evaluate the impact on cell permeability. The results show that lipophilicity could play an important role for the interference with TJ and that the mechanism is independent from the ion channel TRPV-1 and hence on the flux of calcium into the cells. In summary, we synthesized 4 derivatives of capsaicin of lower lipophilicity and compared their properties with other well-known vanilloids. We show that these compounds are able to enhance the permeability of a hydrophilic macromolecule, by opening the TJ for a shorter time than capsaicin. This behavior is dependent on the lipophilicity of the molecule. Understanding of these phenomena may lead to better control of administration of therapeutic molecules

Chemistry of Tetrathiomolybdate and Tetraselenotungstate: Applications in Carbohydrate and Peptide Chemistry

(A) The first report on the application of tetrathiomolybdate, $MoS_4 ^{2,-} 1$ in carbohydrate chemistry appeared in 1997 towards the synthesis of sugar disulfides. More recently use of tetraselenotungstate, $WSe_4 ^{2,-} 2$ towards the synthesis of sugar diselenides has been published. The reagents 1 or 2 work very well for the synthesis of disulfides and diselenides respectively from the corresponding sugar halides. (B) The formation of disulfides and diselenides has been applied in the efficient synthesis of cystine, selenocystine, and their higher homologues like homo and bis-homo amino acid derivatives from natural amino acids. The generality of the reaction has been studied by capping various groups to amino and carboxyl components of canonical amino acids

Propargyloxycarbonyl (Poc) as a protective group for the hydroxyl function in carbohydrate synthesis

The propargyloxycarbonyl (Poc) group can be used for the selective protection of the hydroxyl function in carbohydrates and can be removed under neutral conditions using tetrathiomolybdate MoS42- (1) in CH3CN at room temperature. Under the conditions of deprotection benzylidine acetals, benzyl ethers, acetyl and levulinoyl esters, and allyl and benzyl carbonates are left untouched. It has also been shown that the new protective group (Poc) is compatible with acidic, basic, and also glycosylation conditions

Propargyloxycarbonyl (Poc) as a protective group for the hydroxyl function in carbohydrate synthesis

The propargyloxycarbonyl (Poc) group can be used for the selective protection of the hydroxyl function in carbohydrates and can be removed under neutral conditions using tetrathiomolybdate MoS_4 \hspace{1mm}^{2-} (1) in $CH_3CN$ at room temperature. Under the conditions of deprotection benzylidine acetals, benzyl ethers, acetyl and levulinoyl esters, and allyl and benzyl carbonates are left untouched. It has also been shown that the new protective group (Poc) is compatible with acidic, basic, and also glycosylation conditions

A Ring Expansion–Glycosylation Strategy toward the Synthesis of Septano-oligosaccharides

A one-pot ring-expansion–glycosylation reaction was performed using 1,2-cyclopropanated sugars as glycosyl donors and carbohydrate <i>O</i>-nucleophiles as acceptors to provide septanohexose mimics of pyranose and furanose derivatives. The methodology was successfully extended to the synthesis of septano-oligosaccharides by adopting a divergent strategy as well as an iterative protocol

Mer gymnastik i skolan lönar sig.

Electrophilic ring opening of spiro-cyclopropanecarboxylated sugars followed by reaction with DBU revealed interesting ring-contraction and ring-expansion reactions depending on the substrate and the kind of hydroxyl protective group present adjacent to the spiro center. A stereoselective method for accessing a new class of carbon chain extended keto-furanoses and C-glycosylated bicyclic compounds is reported

Synthetic Applications of Carbohydrate-derived Donor-Acceptor Cyclopropanes

In this account, we elaborate our group's contribution towards understanding the chemistry of carbohydrate-derived donor-acceptor (DA) cyclopropanes. Our work was mainly focused on the ring opening of these versatile chiral synthons under the influence of Lewis acid promoters like electrophilic halogen species, TMSOTf, BF3.OEt2, etc. We studied various modes of ring opening on these DA cyclopropanes, envisaging the access to intriguing molecular architectures. These modes of reaction of the DA cyclopropanes can be controlled by strategically introducing an electron-withdrawing group (EWG) onto the cyclopropane ring, which could direct the ring cleavage by polarizing the cyclopropane C-C bond. Our studies also revealed that the ring opening is sluggish in the absence of an EWG. Using this concept, we demonstrated the synthesis of various biologically interesting molecular skeletons, viz., glycoamino acids (GAA), GAA nucleotides, -levoglucosan amino acid, and septano-oligosaccharides, with high selectivity. We also applied our understanding to the first stereoselective synthesis of (S)-(-)-longianone and confirmed its absolute configuration. Apart from the inherently activated DA cyclopropanes, we introduced the in situ generation of DA cyclopropanes, starting from vinylcyclopropanes (VCPs). The ring-opening and ring-expansion chemistry of these easily accessible synthons was studied. The chemistry developed for carbohydrate-fused cyclopropanes was also applied for carbohydrate-derived spiro-cyclopropanes. The Lewis-acid-mediated ring opening of spiro-DA-cyclopropanes enabled easy access to fused furopyrans and spirolactones

Chemistry of Tetrathiomolybdate and Tetraselenotungstate: Applications in Carbohydrate Chemistry

An efficient one pot synthesis of thio and selenolevoglucosans from 1,6-diactivated carbohydrate derivatives has been achieved using benzyltriethylammonium tetrathiomolybdate, $[BnNEt_3]_2MoS_4$, as a sulfur transfer reagent and tetraethylammonium tetraselenotungstate, $[Et_4N]_2WSe_4$, as a selenium transfer reagent, respectively. The methodology has also been extended to the synthesis of 1,5-epithio and 1,5-episeleno pentoses

Selective reduction of anomeric azides to amines with tetrathiomolybdate: Synthesis of beta-D-glycosylamines

A number of beta-D-glycosyl azide derivatives undergo reduction on treatment with tetrathiomolybdate to produce the corresponding beta-D-glycosylamines exclusively without anomerization under very mild and neutral reaction conditions. Acetyl, allyl, benzoyl, and benzyl protective groups are left untouched under the reaction conditions. An exclusive selectivity in the reduction of anomeric azides is observed, while the C-2 and C-6 azides are left untouched