A Solid-Support Methodology

The cube-like molecule was constructed in solution, which does not afford adequate control over the synthetic process. Consequently, we have developed a sol-id-support-based methodology, which is much more convenient (Y. Zhang and Seeman 1992). A primary advantage is that growing molecules are isolated from one another on the support, so that the simplicity and specificity of sticky-ended 

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Zhang, Y., Seeman, N.C. (1992) A solid-support methodology for the construction of geometrical objects from DNA. /. Am. Chem. Soc. 114, 2656-2663. 

To achieve a higher control over the synthesis of the intermediates and thus the final target, a solid-support methodology (Figure 18(a)) was developed [17]. The synthesis of a quadrilateral starts with... 

When the 1,3-dicarbonyl substrate reacts twice via its activated methylene due to the presence of heteroatoms blocking the enolization process on other positions, spiranic systems are formed in the presence of two equivalents of aldehyde and an equivalent of urea (Scheme 15) [85]. The reaction can be promoted either in acetic acid as solvent or neat under microwave irradiations or in the presence of H3PW12O40 as catalyst. Finally, this technique for generating spiroheterocyclic products has been transferred to solid-supported methodology by immobilizing the 1,3-dicarbonyl partner onto a resin [86]. 

Synthetic oligonucleotides are very important tools in the study and manipulation of DNA, including such techniques as site-directed mutagenesis and DNA amplification by the polymerase chain reaction (PCR). The techniques for chemical synthesis of oligonucleotides have been highly developed. Very efficient and automated methodologies based on synthesis on a solid support are used widely in fields that depend on the availability of defined DNA sequences.152... 

The above described methodology was found to be very useful in a solid-supported synthesis of pyrazoles and pyrimidines via propenones developed by Westman and co-workers35 (Scheme 5.19). Merrifield resin was reacted with methylamine in water at 150°C for 10 min to form the solid-supported benzylmethylamine (3) in high yield (86% yield, 1.08 mmol/g based on elemental analysis). After washing, the resin was treated with 5 equiv. DMFDEA and 5 equiv of 4-phenoxyacetophenone at 180°C for 10 min in DMF to form the solid supported benzyl methyl aminopropenones (4). 

Coiled-coil polypeptides can also be prepared by stepwise fragment condensations on a solid support. A unique feature of the heptad sequence used in de novo designed coiled coils is that a Gly residue can be incorporated as the C-terminal residue of the heptad sequence without the ability of the polypeptide to form stable two-stranded a-helical coiled coils being affected. Although the fragment condensation methodology can be performed with minimal... 

To address the purification issue, which frequently is a bottle-neck in the fast microwave chemistry, a solid-phase catch and release methodology was utilized in a two-component, two-step synthesis of l-alkyl-4-imidazolecarboxylates [45]. In the first step, a collection of isonitriles 25 was immobilized onto a solid support by the reaction with the commercially available N-mclhyl aminomethylated polystyrene 26. Subsequent treatment with various amines brought about simultaneous derivatization and release of the desired imidazoles 27 back into solution. Significantly, only derivatized material was released from the resin, thus ensuring high purity of the desired product. Both steps of the reaction were substantially accelerated by microwave dielectric heating, resulting in the overall reaction time reduction from 60 hours to 70 minutes (Scheme 18). 

Benzothiazoles are most commonly prepared by the ring closure of o-aminobenzothiazoles. This methodology has been well reviewed in both CHEC(1984) <1984CHEC(6)235> and CHEC-II(1996) <1996CHEC-II(3)373>. Typically an o-aminothiophenol is reacted with a suitable electrophile such as an aldehyde, a carboxylic acid, or an ester in a suitable solvent at reflux to provide the desired benzothiazole. Acid chlorides have also been used. The use of esters usually requires harsh conditions, but when the ester is bound to a solid support 241, it has been found that the addition of o-aminothiophenol in the presence of AlMes or Et2AlCl as Lewis acid produces the benzothiazole 242 in what has become known as a smart cleavage reaction (Scheme 97) <2004TL313>. 

Theoretical studies of the properties of the individual components of nanocat-alytic systems (including metal nanoclusters, finite or extended supporting substrates, and molecular reactants and products), and of their assemblies (that is, a metal cluster anchored to the surface of a solid support material with molecular reactants adsorbed on either the cluster, the support surface, or both), employ an arsenal of diverse theoretical methodologies and techniques for a recent perspective article about computations in materials science and condensed matter studies [254], These theoretical tools include quantum mechanical electronic structure calculations coupled with structural optimizations (that is, determination of equilibrium, ground state nuclear configurations), searches for reaction pathways and microscopic reaction mechanisms, ab initio investigations of the dynamics of adsorption and reactive processes, statistical mechanical techniques (quantum, semiclassical, and classical) for determination of reaction rates, and evaluation of probabilities for reactive encounters between adsorbed reactants using kinetic equation for multiparticle adsorption, surface diffusion, and collisions between mobile adsorbed species, as well as explorations of spatiotemporal distributions of reactants and products. 

The biocatalyzed phenylacetyl removal can be carried out using both solubilized or immobilized substrates1771. The latter methodology has been developed using controlled pore glass (CPG) as a solid support (Fig. 18-7). 

A method has been developed that combines the advantages of solid-supported catalyst extraction and solution-phase reactivity. By preparing a palladium complex bearing an anthracene tag, this can then be attached to a solid support via a chemoselective Diels-Alder cycloaddition to sequester the palladium catalyst along with any dissociated phosphine or phosphine oxide at the end of the reaction, leaving the desired catalysis product in the solution. The basis of the methodology is shown in Scheme 15. 

Another novel approach to labelling molecules with carbon-11 has been published by Somawardhana, Sajjad and Lambrecht . These workers have absorbed one of the reactants required for the synthesis on a solid support and the reaction has been done by adding the other reagents to the solid support and heating the mixture in a sealed vial. One example illustrating their methodology is the formation of [l- C]putrescine. The H CN is trapped on a potassium-hydroxide-coated silica gel. Then, acrylonitrile is added, and the reaction tube sealed at both ends. After the tube had been heated at 75 °C for 5 minutes, the Michael addition product was eluted from the solid support and the solvent evaporated. Finally, the nitrile groups were reduced with a borane-dimethylsulphide complex in THF (equation 77). The total reaction time was less than 40 minutes and the product was obtained in a 53% radiochemical yield. 

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