A solid-supported acidic oxazolium perchlorate as an easy-handling catalyst for the synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation

A solid-supported acidic oxazolium perchlorate was investigated as a heterogeneous catalyst in N-glycosylation reactions using silylated modified pyrimidines and an acylated ribose or glucose to afford the corresponding pyrimidine nucleosides. This salt is a nonhygroscopic and stable powder whose activity is comparable to that of 2-methyl-5-phenylbenzoxazolium perchlorate. A reaction with this polymer catalyst can be conducted on a gram scale. Reusability of the solid-supported catalyst was also investigated.     

Microwave assisted "click" chemistry for the synthesis of multiple labeled-carbohydrate oligonucleotides on solid support

A versatile approach has been developed for the multiple labeling of oligonucleotides. First, three linkers as a H-phosphonate monoester derivative were condensed on a solid-supported T12 to introduce H-phosphonate diester linkages which were oxidized in the presence of propargylamine. Second, three galactosyl azide derivatives were conjugated to the solid-supported three-alkyne-modified T12 by a 1,3-cycloaddition so-called "click chemistry" in the presence of Cu(I) assisted by microwaves.     

Development of a novel environmentally friendly electrolytic system by using recyclable solid-supported bases for in situ generation of a supporting electrolyte from methanol as a solvent: application for anodic methoxylation of organic compounds

We have successfully developed a novel environmentally friendly electrolytic system using recyclable solid-supported bases for in situ generation of a supporting electrolyte from methanol as a solvent. It was found that solid-supported bases are electrochemically inactive at an electrode surface. It was also found that solid-supported bases dissociate methanol into methoxide anions and protons. Therefore, in the presence of solid-supported bases, it was clarified that methanol serves as both a solvent and a supporting electrolyte generated in situ. Anodic methoxylation of various compounds with solid-supported bases was carried out to provide the corresponding methoxylated products in good to excellent yields with a few exceptions. The methoxylated products and the solid-supported bases were easily separated by only filtration, and the desired pure methoxylated products were readily isolated simply by concentration of the filtrates. The separated and recovered solid-supported bases were recyclable for several times.     

Development of an electrolytic system using solid-supported bases for in situ generation of a supporting electrolyte from methanol as a solvent

We have successfully developed a novel electrolytic system using solid-supported bases for in situ generation of a supporting electrolyte from methanol as a solvent. Anodic methoxylation of phenyl 2,2,2-trifluoroethyl sulfide using solid-supported bases was carried out to provide the alpha-methoxylated product in good to excellent yields. The alpha-methoxylated product and solid-supported bases were easily separated by only filtration, and the separated solid-supported bases were recyclable. Anodic methoxylation of phenyl 2,2,2-trifluoroethyl sulfide was successfully carried out 10 times by the recycling of silica gel-supported piperidine in good yields.     

Segregation of separate steps in chromium-catalyzed reactions for convenience and mechanistic analysis

[structure: see text] We have developed an apparatus for carrying out redox-coupled chromium-manganese or chromium-zinc reactions on solid-supported substrates which allows recycling of the stoichiometric reductant. In addition to providing a greatly simplified procedure for these reactions, we observe striking differences in the recyclability of Mn and Zn. A preliminary extension of the methodology to the catalytic coupling of allylchromium reagents with solid-supported aldehydes is also reported.     

Solid-phase synthesis of trisubsituted guanidines

The solid-phase library synthesis of trisubstituted guanidines was accomplished. Amines were loaded onto the 4-formyl-3,5-dimethoxyphenoxymethyl linker via reductive amination. Subsequent acylation with Fmoc-4-aminomethylbenzoic acid followed by Fmoc deprotection gave solid-supported primary amines. Alternatively, sulfonylation of resin-bound secondary amines with 4-cyanobenzenesulfonyl chloride followed by borane reduction also gave solid-supported primary amines. Both resins were acylated with isocyanates to furnish solid-supported ureas. Dehydration of ureas with p-toluenesulfonyl chloride in pyridine gave solid-supported carbodiimides. Nucleophilic addition of amines to the carbodiimide bond followed by cleavage off the solid support gave trisubstituted guanidines.     

Parallel synthesis of a vitamin D(3) library in the solid-phase.

A highly efficient synthesis of the vitamin D(3) system on solid support is described. Two synthetic strategies for the solid-phase synthesis of vitamin D(3) were developed. One is for 11-hydroxy analogues, and the other is for most other synthetic analogues. In the latter strategy, the sulfonate-linked CD-ring 58 was initially immobilized on PS-DES resin to give solid-supported CD-ring 63 (Scheme 10). Similarly, solid-supported CD-ring 63 was prepared by attachment of the CD-ring 10 to the chlorosulfonate resin 64. The vitamin D(3) system was synthesized by Horner-Wadsworth-Emmons reaction of the A-ring phosphine oxide to a solid-supported CD-ring, followed by simultaneous introduction of the side chain and cleavage from resin with a Cu(I)-catalyzed Grignard reagent. Parallel synthesis of the vitamin D(3) analogues was accomplished by a split and pool methodology utilizing radio frequency encoded combinatorial chemistry, and a manual parallel synthesizer for side chain diversification and deprotection. Additionally, we demonstrated the synthesis of various A-rings in a similar protocol for efficient preparation of building blocks.     

Lipase-catalyzed kinetic resolution on solid-phase via a "capture and release" strategy

The lipase-catalyzed kinetic resolution of (R/S)-3-phenylbutyric acid 2 using solid-supported cyclohexane-1,3-dione (CHD) 6 is described. In each case the predominant enantiomer observed, after cleavage from the resin, was (R)-(-)-3-phenylbutyric acid (R)-2 (ee > 99%) rather than the expected (S)-enantiomer of 2. This observation is in contrast to the fact that Chromobacterium viscosum lipase shows high enantiospecificity for the (S)-enantiomer in the corresponding solution-phase hydrolysis reactions. The (R)-acyl group was subsequently released from the resin by NaOH hydrolysis, and the yield of the reaction could be improved by triple acylation of the resin.     

Phosphine-free perfluoro-tagged palladium nanoparticles supported on fluorous silica gel: application to the Heck reaction

The immobilization of phosphine-free perfluoro-tagged palladium nanoparticles Pd-1 on fluorous silica gel (FSG) and their utilization in the Heck reaction have been investigated. High yields of vinylic substitution products have been obtained. Recycling studies have shown that the solid-supported palladium catalyst can be readily recovered and reused several times without significant loss of activity. Reactions and recovery of the solid-supported palladium catalyst system can be carried out in the presence of air, without any particular precaution.     

One-pot preparation and activation of glycosyl trichloroacetimidates: operationally simple glycosylation induced by combined use of solid-supported, reactivity-opposing reagents

By the combined use of solid-supported reactivity-opposing reagents, that is, basic PTBD and acidic Nafion^®-SAC resins, sequential reactions consisting of glycosyl trichloroacetimidate formation and glycosylation can be effected in a one-pot operation starting from 1-O-unprotected sugars. The solid-supported reagents can be introduced into the reaction vessel either sequentially or, more conveniently, in a `one-shot' manner in comparable yields.     

Polymer-supported O-methylisourea: a new reagent for the O-methylation of carboxylic acids

[reaction: see text] A solid-supported O-methylisourea reagent has been prepared in one step starting from commercially available solid-supported carbodiimide. The isourea reagent has been successfully used for the preparation of methyl esters from the corresponding carboxylic acids. The crude products obtained after resin filtration and solvent evaporation are generally obtained in >98% purity.     

Vacuum-driven anionic ligand exchange in Buchmeiser-Hoveyda-Grubbs ruthenium(II) benzylidenes

Vacuum-driven anionic ligand exchange of a perfluorocarboxylic acid with ruthenate-bound perfluorocarboxylates is demonstrated and allows for a novel entry to solid-supported ruthenium benzylidenes.     

Rapid activation of the melibiose permease MelB immobilized on a solid-supported membrane

Rapid solution exchange on a solid-supported membrane (SSM) is investigated using fluidic structures and a solid-supported membrane of 1 mm diameter in wall jet geometry. The flow is analyzed with a new technique based on specific ion interactions with the surface combined with an electrical measurement. The critical parameters affecting the time course of the solution exchange and the transfer function describing the time resolution of the SSM system are determined. The experimental data indicate that solution transport represents an intermediate situation between the plug flow and the Hagen-Poiseuille laminar flow regime. However, to a good approximation the rise of the surface concentration can be described by Hagen-Poiseuille flow with ideal mixing at the surface of the SSM. Using an improved cuvette design, solution exchange as fast as 2 ms was achieved at the surface of a solid-supported membrane. As an application of the technique, the rate constant of a fast electrogenic reaction in the melibiose permease MelB, a bacterial ( Escherichia coli) sugar transporter, is determined. For comparison, the kinetics of a conformational transition of the same transporter was measured using stopped-flow tryptophan fluorescence spectroscopy. The relaxation time constant obtained for the charge displacement agrees with that determined in the stopped-flow experiments. This demonstrates that upon sugar binding MelB undergoes an electrogenic conformational transition with a rate constant of k approximately 250 s (-1).     

固载化试剂和催化剂及其在液相组合合成中的应用

固载化试剂、催化剂及清洁树脂在液相合成中的应用, 极大地方便了液相合成的后处理, 提高了工作效率, 为液相平行组合合成提供了基础. 重点综述了近年来固载化试剂和催化剂在液相组合合成及多步液相合成中应用进展情况.     

A new approach to synthesis of 2-sulfonylamino-1,2,4-triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines

A procedure for synthesis of 2-sulfonylamino-1,2,4-triazolo[1,5-a]pyrimidines by sulfonylation of 2-amino-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines, followed by oxidation of intermediate 2-sulfonylamino-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines, was suggested.     

Scanning force microscopy based rapid force curve acquisition on supported lipid bilayers: experiments and simulations using pulsed force mode.

In situ pulsed force mode scanning force microscopy (PFM-SFM) images of phase separated solid-supported lipid bilayers are discussed with the help of computer simulations. Simultaneous imaging of material properties and topography in a liquid environment by means of PFM-SFM is severely hampered by hydrodynamic damping of the cantilever. Stiffness and adhesion images of solid-supported membranes consisting of cholesterol, sphingomyelin, and 1,2-dioleyl-phosphatidylcholine obtained in aqueous solution exhibit contrast inversion of adhesion and stiff. ness images depending on parameters such as driving frequency, amplitude, and trigger setting. Simulations using a simple harmonic oscillator model explain experimental findings and give a deeper insight into the way PFM-SFM experiments have to be performed in order to obtain interpretable results and hence pave the way for reliable material contrast imaging at high speed.     

Cross coupling reactions of organozinc iodides with solid-supported electrophiles: synthesis of 4-substituted benzoic and 3-substituted (E)- and (Z)-propenoic acids and amides

The solid-supported iodobenzoic acid derivatives 8-10 were coupled with a range of organozinc reagents 1-4 under palladium(o) catalysis. The coupled products released by acidic cleavage with TFA were obtained in high purities after recrystallisation. Analogous coupling of solid-supported (E)- and (Z)-3-iodoacrylic acids 18a, 18b, 19 and 20 gave (E)- and (Z)-alpha,beta-unsaturated acids and amides 21-27 stereospecifically.     

Simplified methods for preparation of microbial fatty acids for analysis by gas chromatography with electron-capture detection

Analysis of bacterial metabolites and constituents by gas chromatography (GC) with frequency-pulsed electron-capture detection (FPECD) has been suggested as an approach to rapid identification of infection in man. In such methods conversion of analytes to electrophoric derivatives is obligatory. Present methods for analysis of microbial carboxylic acids by GC-FPECD use trichloroethylation. In order to simplify and possibly automate such sample preparation procedures, we investigated pentafluorobenzylation via extractive alkylation and via solid-supported reagents. The sensitivity in terms of minimum amounts of bacteria detectable were determined for the trichloroethyl and pentafluorobenzyl derivatives and results from solid-supported reagents were compared to extractive alkylation.     

Synthesis of pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]pyrimidines

Starting from 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones, a synthesis pathway to the tricyclic pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines is described. Reaction of 1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-ones with phosphoryl chloride afforded the corresponding 4-chloro-1H-pyrazolo[3,4-d]pyrimidines. Treatment of these compounds with hydrazine hydrate at reflux temperature gave the hydrazino derivatives, which were subsequently cyclized to the titled compounds on heating with orthoesters in ethanol. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

Organic synthesis in a changing world

This article is based on a lecture presented to the Chemical Society of Japan at Wasada University on March 27, 2002, by Professor Steven V. Ley. The lecture, "Organic Synthesis in a Changing World," was a comprehensive account of the ongoing research efforts of professor Ley's group in the development and application of solid-supported reagents and scavengers for use in organic synthesis.