Letters in Organic Chemistry - Volume 8, Issue 5, 2011

The synthesis of a mannose-bearing disaccharide containing a thiol spacer at the reducing end was carried out to provide a tethered sugar suitable for attaching to gold nanoparticles. An array of such sugars is designed to mimic carbohydrates involved in cell-surface interactions. The molecule was constructed via Schmidt glycosylation of an appropriately protected glycosyl donor and an acceptor, followed by removal of protective groups and reductive amination to introduce a protected thiol spacer at the reducing end of the glycan. A new finding that the anomeric reductive amination is capable of concomitantly removing a neighboring N-acetyl group was also observed. Subsequent removal of the thiol protective group and purification of the product gave the target disaccharide in a satisfactory yield.

The resolution of 2-isobornyl-4-methylphenol (±)-1 via diastereomers was carried out. The enantioenriched phenols (+)-1, (-)-1 and morpholinomethyl derivatives (+)-6, (-)-6 were tested for their cytotoxic and anti-inflammatory activities in comparison with their racemates. The anti-inflammatory activity comparable to that of indomethacin estimated for the racemic amine (±)-6 is due to the enantiomer (+)-6. The enantiomer (-)-6 exhibits a moderate cytotoxicity against the human cancer cell line melanoma (MS) while enantiomer (-)-1 demonstrates the inhibitory activity against the human cancer cell line lung carcinoma (A549). The absolute configuration of the diastereomeric intermediates and separated phenols were established by X-ray diffraction analysis.

The dye-sensitized photooxygenation of 2,5-bis(glycosyl)furans followed by warming up to r.t. provides 1,1'- linked disaccharides separated by a functionalized spacer. Asymmetrical disubstituted glycosyl furans give the corresponding Bayer-Villiger type-rearranged products in a molar ratio depending on the sugars and the protecting groups. The migratory aptitudes have been rationalized by both theoretical calculations and experimental data. The 1,1'- disaccharides obtained are new sugar derivatives structurally related to some mimetics of Sialyl Lewis X.

A novel reaction between saccharin (1,2-benzisothiazole-3(2H)-one-1,1-dioxide, o-sulfobenzimide, or obenzoic sulfimide) and cyanide to afford an unexpected compound, 2-(cyanosulfonyl)benzamide, has been described. Cyanide ion proved to attack the sulfonyl group of o-sulfobenzimide over 170 °C to open the ring and to add to form a new C-S bond. This is an unexpected reaction, as the leading theory of chemical reaction predicts cyanide to be too weak to react with sulfonyl groups. The spectroscopic data and the elemental analyses confirm the structure of the resulted compound and support the mechanism of reaction. The reaction pathway is important from the theoretical point of view, however it might serve both preparative and analytical purposes.

A series of novel substituted γ-amino acids has been catalytically prepared by a one-pot reaction of substituted imines and homoenolates. The efficiency of the novel direct route has been found to depend on the nature of amine being either aliphatic or aromatic. Additionally, the influence of aromatic substituents has been investigated.

A copper-catalyzed coupling reaction of aryl halides with various aromatic cyclic secondary amines in DMSO has been developed efficiently. The versatile and efficient copper catalyst system is of wide-spread and practical application in cross-coupling reactions.

A practical method to prepare selected deuterated hydroxybenzoic acids was developed. A hydroxybenzoic acid was dissolved or suspended in deuterium oxide (D2O), then deuterium chloride (DCl) was added to adjust the pD to 0.32, and the mixture was refluxed under nitrogen for one to six hours. After removing D2O and DCl by lyophilization, 2,6-dihydroxybenzoic-3,5-d2 acid, 3,5-dihydroxybenzoic-2,4,6-d3 acid, 3,5-dimethoxy-4-hydroxybezoic-2,6-d2 acid, and 3,4,5-trihydroxybenzoic-2,6-d2 acid were obtained quantitatively. Aromatic carbons with double substituent effects of hydroxy or methoxy groups were selectively deuterated. It was shown that the deuterium exchange reactions, which were electrophilic substitution reactions of deuterium cations to the aromatic carbons on the hydroxybenzoic acids, were regulated by the substituent effects. Deuteriums on all aromatic carbons were stable under a physiological condition and were detected in plasma by mass spectrometry analysis after oral administration to rats.

The paper highlights an efficient methodology based on consecutive radical reaction for the preparation of cyclonucleoside derivatives. The reactions were performed in organic and aqueous media, using common and efficient free radical hydrogen donors in the range of innovative and conventional initiation conditions to afford good to excellent yields of corresponding cyclonucleosides. The mechanistic aspects of the transformations are also addressed.

The spirostanic side chain of pennogenin can be quantitatively transformed under mild acidic conditions in a 22-oxocholestanic framework through a one step procedure. This methodology is the shortest way to afford the 3,16,26- trihydroxy-22-oxocholestanic derivative, analogue of the protected aglycon of the potent antitumor agent OSW-1. The primary hydroxyl group at C-26 could be selectively transformed.

This work describes cheap and simple methods to obtain biological active furano naphthoquinones in good yields. Hydroxyiso-β-lapachone (3) was obtained in 61% yield from the reaction of lapachol (1) and MCPBA in dichloromethane using Na2HPO4 as the base. Reaction of 1 with MCPBA, followed by the addition of KOH/DMSO furnished both stenocarpoquinone-A (2) and avicequinone-C (5) in 20% yield. Using oxone/acetone and NaHCO3, stenocarpoquinone-B (4) was obtained in 50% yield. The biological assays using tumor cell lines showed that 1 is, in general, less toxic than its derivatives. Compounds 4 and 5, on the other hand, were strongly active against the four tested tumor cells.

The catalyst-free allylation of isatins with allyltrichlorosilane was performed smoothly in DMF under mild conditions and moderate to excellent yields (60%-94%) were obtained. This protocol provided a new and efficient approach for the preparation of 3-allyl-3-hydroxy-2-oxindoles.

The novel lariat calix[4]-1,3-aza-crowns with chiral amino acids groups as branched chain (5a) and (5b) were synthesized via “1+1” addition of calix[4]-1,3-substituted benzaldehyde derivative (4) and amino acids hydrazide derivatives (3a) and (3b) in yields of 70% and 75%, respectively.

Conditions have been found for an efficient regioselective β-hydrosilylation of allylbenzene, 2-allyl-1- trimethylsiloxybenzene, 4-allyl-1,2-(methylenedioxy)benzene, allylpentafluorobenzene, and 4-allyl-2-methoxy-1- trimethylsiloxybenzene with D4H in the presence of Karstedt's-catalyst or platinum black under mild conditions leading quantitatively to functionalized tetramethylcyclosiloxanes 3.

A highly-efficient method for the copper- and solvent-free coupling reaction of acid chlorides and terminal alkynes catalyzed by diatomite-supported palladium(II) salophen complex is described. Acid chlorides are easily coupled with terminal alkynes, giving good to high yields in the presence of a low catalyst loading (1 mol% Pd) in DIEA at room temperature under aerobic conditions. After centrifugation, the supported catalyst is able to be recycled and reused for several times with only a slight decrease in activity.