Development of a new traceless aniline linker for combinatorial solid-phase parallel synthesis of rod-shaped liquid crystals with an azomethine linkage

A new traceless linker was developed to synthesize a library of 28 compounds possessing an azomethine linkage using combinatorial solid-phase parallel synthesis. The loading of the substrates on a solid support and cleavage from the solid support were performed by an imine synthesis and by imine-exchanged process in the mild conditions, respectively. Products with a thioester group exhibited liquid crystalline properties with the higher transition temperatures than the others.     

Solid-phase combinatorial synthesis of benzothiazoles, benzimidazoles, and benzoxazoles using a traceless linker

New methodology for the solid-phase synthesis of benzothiazoles, benzimidazoles, and benzoxazoles has been developed by using a traceless 4-alkoxy-aniline linker. The desired products were released from the polymer support by imine-exchange process coupled with air oxidation. Combinatorial library consisting of 36 members has been synthesized using this linker. The yields are low to good, which highly depend on the building blocks. Recycling of the polymer support was also investigated.     

Development of the traceless phenylhydrazide linker for solid-phase synthesis

The hydrazide group is a new oxidatively cleavable traceless linker for solid-phase chemistry. It can be readily introduced by hydrazide formation between a carboxy-functionalized resin and different substituted hydrazines. In order to achieve high yields in this step, new carboxylic acid resins were developed that are not prone to undesired imide formation upon activation of the carboxylic acid. The polymer-bound acyl hydrazides were successfully employed in various transformations, namely Heck, Suzuki, Sonogashira, and Stille couplings, as well as Wittig and Grignard reactions. Traceless release of the coupling products from the solid support is achieved selectively under mild conditions and in high purity by oxidation of the aryl hydrazides to acyl diazenes with Cu(II) salts or N-bromosuccinimide (NBS) and subsequent nucleophilic attack of the acyl diazene intermediates. Traceless cleavage by oxidation with NBS can be carried out as a two-step process in which stable acyl diazenes are first generated by treatment with NBS in the absence of a nucleophile. After removal of the reagents by simple resin washing, the traceless release is effected by the addition of methanol, which leads to products of high purity without any additional separation steps.     

Solid-phase synthesis of liquid crystalline isoxazole library

Combinatorial library of isoxazoles was prepared by 1,3-dipolar cycloaddition on solid support. p-Cyano derivatives showed nematic and/or smectic A phases. A bilayer smectic phase for 2h is proposed by the combination of molecular mechanics calculation and X-ray diffraction experiment.     

A facile solid-phase synthesis of 3,4,6-trisubstituted-2-pyridones using sodium benzenesulfinate as a traceless linker

A facile and traceless solid-phase synthesis of 3,4,6-trisubstituted-2-pyridones has been developed using polystyrene sodium benzenesulfinate resin. The chemistry is applicable to combinatorial library synthesis.     

A new versatile linker for the solid-phase synthesis of secondary amines

A novel linker for the solid-phase synthesis of secondary amines based on an intramolecular cyclization was developed. The linker allows for a stepwise built-up of the secondary amines on the support. The feasibility was demonstrated in the parallel synthesis of a small set of different secondary amines.     

New selenyl linker for solid-phase synthesis of dehydropeptides

A novel linker possessing selenocyanate and masked carboxylic acid was developed for the solid-phase synthesis of dehydropeptides. This linker was used to demonstrate the synthesis of the model compound of RGD-conjugated dehydropeptide.     

Multistep solid-phase synthesis of an antibiotic and receptor tyrosine kinase inhibitors using the traceless phenylhydrazide linker

The hydrazide group is an oxidatively cleavable traceless linker for solid-phase chemistry. This linker technology was used to develop a multistep solid-phase synthesis of an antibiotic that is active against Mycobacterium tuberculosis. Furthermore, we describe an efficient method for the traceless synthesis of 2-aminothiazoles that display dual inhibitory activity against the receptor tyrosine kinases VEGFR-2 and Tie-2. The synthesis method proceeds through 9 steps on the solid phase and should give access to a much larger library of 2-aminothiazoles, from which a new class of anti-angiogenesis drugs may be developed.     

Synthesis of a new troponoid liquid crystalline library on solid support

Five types of troponoids including 40 molecules were prepared by means of palladium(0)-catalyzed carbonylation and successive acylation or benzoylation after immobilization of 2-methoxy-5-trifluoromethylsulfonyloxytropone on solid support. Four types of them showed mesophases. The final products have enough purity to detect their mesomorphic properties.     

Ugi four-center three-component reaction for the parallel solid-phase synthesis of N-substituted thiomopholinones

Starting with resin-bound bifunctional 2-(2-aminoethylthio)acetic, an efficient synthesis of a variety of N-cycloakyl thiomopholinones is described utilizing the Ugi four-center three-component reaction (U-4C-3CR).     

Development of a new linker for the solid-phase synthesis of N-hydroxylated and N-methylated secondary amines

Merrifield resin was modified by the introduction of an ortho-nitrophenylethanal group that served as a linker moiety to attach amines to the resin by reductive amination. Resin-bound tertiary amines were shown to be readily transferred into the respective liberated N-hydroxylated or N-methylated derivatives by either an oxidation/Cope elimination or a permethylation/Hofmann elimination protocol. With these two divergent liberation/derivatization options, the new resin offers new flexibility in the solid phase synthesis of N-modified secondary amines, for instance in spider toxin synthesis.     

Utility of a liquid crystalline diacrylate for bistable switching cholesteric gel displays

We investigated cholesteric liquid crystals containing an anisotropic polymer network created by in situ photo-polymerization of a mesogenic diacrylate. In contrast to previous studies, we used a liquid crystalline diacrylate to achieve bistable switching between the reflecting Grandjean texture and the diffuse scattering focal conic texture. The switching behavior depends considerably on the orientation of the liquid crystal during the polymerization. For polymerization in the Grandjean texture, the response times for switching to the reflecting state were lowered compared to the pure liquid crystal. The chromaticity coordinates indicate that this new type of display is very promising for additive color mixing.     

Polymer-supported thiobenzophenone: a self-indicating traceless ‘catch and release’ linker for the synthesis of isothiocyanates

The use of a thiobenzophenone as a self-indicating linker in the polymer-supported synthesis of isothiocyanates via a traceless ‘catch and release’ strategy is reported. Isothiocyanates were furnished via 1,3-dipolar cycloaddition of nitrile oxides with the polymer-supported thiobenzophenone linker, followed by Lewis acid-assisted fragmentation of the resulting polymer-supported oxathiazole.     

Alternative solvents for elevated-temperature solid-phase parallel synthesis. Application to thionation of amides

A new class of higher-boiling solvents was investigated for elevated-temperature solid-phase parallel synthesis. Extremely low vapor pressures at high temperature and a broader range of solvent effect tuning make this new class of solvents an ideal choice for high-temperature parallel solid-phase synthesis. Benzyl benzoate is identified as a superior high-boiling solvent for parallel solid-phase Lawesson's thionation reactions.     

Gaining diversity in solid-phase synthesis by modulation of cleavage conditions from hydroxymethyl-based supports. Application to lamellarin synthesis

The application of a number of Lewis acids as a cleavage/deprotection method in the solid-phase synthesis of organic molecules can render several analogues, which, after purification, can be submitted for biological evaluation.     

Regioselective synthesis and metallation of tributylstannylfluoropyrazines. Application to the synthesis of some new fluorinated liquid crystals diazines. Part 34

Starting from fluoropyrazine, a general synthetic route including metallation and palladium-catalyzed cross-coupling reactions is described to access to rod-like alkylaryl or diarylpyrazines. Among them, some have liquid crystalline properties.     

A new approach for the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines involving reductive cleavage

A methodology based on reductive cleavage followed by cyclization, for the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines employing DIBAL-H, is described.     

Glass capillary columns with liquid crystalline stationary phases for gas chromatography. The influence of the pretreatment of the inside tube wall

Summary The importance of capillary columns prepared with a liquid crystalline stationary phase are increasing. It is known that the interaction of the liquid crystals molecules with the glass capillary wall may strongly influence selectivity and efficiency of the column. The paper reports on systematic investigations on the correlations between the pretreatment of the inside glass capillary surface, the chemical nature of the liquid crystal and the chromatographic properties of the columns obtained. Two types of matrix were investigated: barium carbonate and barium carbonate with subsequent deactivation with Carbowaxes. Three liquid crystals with different relative polarity (terminal group polarity) and nematic mezophase transitions were used. Deposition of barium carbonate, if necessary, with a secondary Carbowax treatment was found as an excellent capillary wall pretreatment method. Presented at the 15th International Symposium on Chromatography, Nürnberg, October 1984     

A new method for cleavage of silicon-carbon linkers on glass plate supports with applications to solid-phase syntheses on silica resins

We describe herein a novel and facile method for the cleavage of a silicon-based linker on solid-phase supports such as glass plates or silica resin. The linker was efficiently cleaved by oxidation of the silicon-carbon bond (Tamao-Kumada oxidation) to release the functionalized molecule.     

Original loading and Suzuki conditions for the solid-phase synthesis of biphenyltetrazoles. Application to the first solid-phase synthesis of irbesartan

Biphenyltetrazoles are recognized privileged structures. Among them, the therapeutically important class of sartans displays antagonistic activity on AT1 receptors. We have developed a method for anchoring tetrazole derivatives via the heterocycle on a hydroxylated resin using zinc triflate. New Suzuki-Miyaura cross-coupling conditions are developed for the quantitative formation of the phenyl-phenyl bond. Our straightforward synthesis scheme, starting from the conserved phenyltetrazole moiety and ending with the appending of the structurally variable moiety, is well suited to the preparation of sartans and their analogues at a laboratory scale. We thus describe here the first solid phase synthesis of irbesartan, a marketed AT1 antagonist.