A method based on colour coding is presented which allows for the facile deconvolution of multi-component reactions in library synthesis

Development of polyhedral oligosilsesquioxanes as scaffolds for biologically relevant groups (e.g., peptides and carbohydrates). Selective mono- and difunctionalization of these frameworks with biologically relevant groups offers potential drug delivery vehicles

The role of single bead FTIR in the reaction optimization stage of solid-phase combinatorial organic synthesis is reviewed

With the advent of combinatorial chemistry and automated synthesis there has been renewed interest in polymer-supported reactions.[1] However, it is evident from the literature that polymer supports used for other than peptide or nucleotide synthesis are, at present, far from optimized. It is not a trivial matter to identify new supports that are economically viable, exhibit satisfactory physical characteristics and that are inert to the diverse range of reagents/catalysts commonly involved in a multi-step combinatorial synthesis. Herein we describe a new class of resins that meet the criteria stated (vide supra). The resins are based on a set of polytetrahydrofuran (PTHF) cross-linkers and hold significant promise as polymer supports for solid-phase synthesis and combinatorial chemistry.

A representative set of symmetric diacids was coupled onto deprotected TentaGel Rink Amide resin. The symmetric building blocks served as model to complete a synthesis protocol and to switch to a different synthesis paradigm consecutively. The reaction sequence continued in a non-combinatorial step by coupling of a bifunctional reagent (3-aminoacetophenone) to the remaining carboxyfunction of the symmetric diacid. The ketone served as model of a reagent prepared for combinatorial functional group transformation. The arylmethylketone was reacted with a set of aryl- and heteroarylaldehydes to give a,b-unsaturated ketones. Subsequently, guanidine, alkyl-, and arylcarboxamidines were introduced in combinatorial synthesis of substituted pyrimidines by reaction with the a,bunsaturated ketone functionality. The combination of symmetric building blocks and combinatorial functional group transformation created a versatile reaction sequence ideally suited for production of libraries from libraries with added diversity

This poster outlines the preliminary data obtained using microreactor technology, which has the potential to offer enhanced reaction optimisation and combinatorial based synthesis and screening. Initial developments have centred on the synthetic application of microreactors to Suzuki [1] and the well-established Wittig synthesis [2]. This particular poster focuses on the Wittig syntheses, Figure 1 in microreactors and will compare the performance characteristics to traditional batch methodology. The poster outlines the reaction yield data using a continuous flow injection microreactor prepared in borosilicate glass (channel geometries 300 microns wide and 100 microns deep) using photolithographic patterning and modified wet etch techniques [3]. The fabrication method, reaction optimisation and microreactor adaptation, including injection optimisation and reaction stoichiometry alteration (1:1 eq.) are described. The resulting optimised method was used with a variety of aldehydes to demonstrate its general applicability. The work extends into the development of a microreactor that will facilitate combinatorial synthesis and detection using the optimised reaction methodology described earlier, enabling the development of a semi automated combinatorial system with the potential for ultra high throughput operation.

For many years solid polymers have been dominant both in parallel syntheses and as supports for organic reagents.1,2 However, there are a number of major concerns associated with the use of insoluble polymeric derivates under heterogeneous conditions such as lowered reactivities, sideside interactions, extended reaction times and diffision-limited reactivity. The use of soluble matrices3 such as poly(ethylene glycol)4 circumvents these problems while also allowing for routine monitoring of the reaction progress. Additionally, the basis for developing soluble polymer-supported chemistry is quite excellent since known solution-phase reaction conditions are preserved.5,6 Our efforts in this field have included the development of soluble polymer-supported combinatorial libraries,7 catalysts,8 reagents,9-11 linker strategies12,13 and synthetic methodology.14,15 This report details the development and application of a poly(ethylene glycol) bound triarylphosphine reagent and the optimization of a liquid-phase Stille cross-coupling reaction with subsequent generation of a small library of biaryl, heterobiaryl and styryl derivatives in high yields and purity.

In this presentation we report the application of microwave assisted chemistry to the parallel synthesis of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones employing a solventless Biginelli multicomponent condensation protocol. The novel method employs neat mixtures of ß-ketoesters, aryl aldehydes, and urea derivatives with polyphosphate ester (PPE) being used as reaction mediator. Irradiation of these mixtures for 90 s in an unmodified household microwave oven provides dihydropyrimidones in 61-95% yield after aqueous work-up. This protcol was extended towards the parallel synthesis of DHPM compound libraries.

A new procedure for the coupling of phenols to 2-chlorotrityl resins has been developed using polymer bound 2-pyridyl ether derivative 1 as tritylation agent. The method allows the immobilisation of phenols under non-basic conditions and is particularly suited for base sensitive phenolic compounds. Scope and limitation of this new coupling method have been investigated.

The Trident automated synthesizer was successfully employed in a two-step split synthesis of amides, sulfonamides and ureas. The key synthetic step involved the preparation of 24 secondary amines from 4 primary amines and 6 carbonyl compounds using Ti(OiPr)4 and NaBH4. These amines were then used in 192 reactions to synthesize 96 ureas in duplicate and 96 reactions to synthesize 48 amides and 48 sulfonamides. The reaction sequences clearly demonstrate the Trident's ability to perform parallel solution phase synthesis and to handle air-sensitive reagents such as Ti(OiPr)4, alkyl isocyanates, acid chlorides and aryl sulfonyl chlorides.