Solid-phase reversible immobilization

Figure 8.13. Solid-phase reversible immobilization (SPRI) extraction of genomic DNA from blood using magnetic silica beads.

Xu Y, Vaidya B, Patel AB et al (2003) Solid-phase reversible immobilization in microfluidic chips for the purification of dye-labeled DNA sequencing fragments. Anal Chem 75 2975-2984... 

One of the first cross-coupling reactions performed on solid supports was the Stille reaction [250] which is a paUadium-catalyzed reaction of a trialkylaryl or trialkylalkenyl stannane with an aromatic iodide, bromide or triflate. In contrast to the process in liquid-phase, the organotin reagent is easily removed from the solid-phase because of the subsequent washing processes. Immobilized aryl halides have been frequently coupled with aryl and alkenylstannanes, whereas stan-nanes attached to the solid support have been used less frequently for the StiUe reaction. An example is the synthesis of a benzodiazepine library by EUman et al. Recently, a Stille cross-couphng reaction has been employed in the synthesis of al-kenyldiarylmethanes (ADAM) series of non-nucleoside HlV-1 Reverse Transcriptase Inhibitors (Scheme 3.14) [251]. 

A prominent advantage of this assay procedure is the feature that the complex of hapten and labeled antibody was captured on a solid phase (PMP) and separated from the reaction medium before signal determination. This additional step not only reduces interference due to biological specimens but also eliminates the tedious transfer of supernatant, which is essential in conventional immunometric assays. This immunometric assay provided somewhat improved specificity in terms of the cross-reactivities with T2 and reverse T3 (3,3, 5 -L-triiodothyronine). The authors speculated that the dissociation rate of the antibody-cross-reactant complex would be faster than that of an antibody-analyte complex thus the former binding would be preferentially substimted by T2 immobilized on CPG. 

Trityl resins are particularly suitable for immobilization of nucleophilic substrates such as acids, alcohols, thiols, and amines. They are quite acid-sensitive and are cleavable even with acetic acid this is useful when acid-labile protecting groups are used. The stability of trityl resin can be tailored by use of substituted arene rings, as shown by chlorotrityl resin, which furnishes a more stable linker than the trityl resin itself. Steric hindrance also prohibits formation of diketopiperazines during the synthesis of peptides. Orthogonality toward allyl-based protective groups was demonstrated in the reverse solid-phase peptide synthesis of oligopeptides [30] (Scheme 6.1.4). 

In this subsection, we describe a couple of examples taken from the recent literature, in which the Baylis-Hillman reaction has been employed for the construction of new carbon-carbon bonds. The Baylis-Hillman reaction proceeds in a catalytic cycle propagated by a nucleophilic catalyst (584). The nucleophilic catalyst initiates the cycle by Michael addition to a double bond bearing an EWG (586 or 590). The carbon a to the EWG is acidic and may react with an electrophile. Finally, the nucleophilic catalyst is eliminated, completing the cycle (Scheme 122). The most frequently used catalysts are quinuclidine, DABCO, phosphines, thiopheno-lates, and selenophenolates. The reaction rate of a catalytic Baylis-Hillman reaction approaches a maximum at a certain temperature and declines upon further heating, as the equilibrium concentration of (587) becomes very small. In the first example, the electrophilic component of the reaction was immobilized on a solid phase and the nucleophile was in solution, while in the other example the situation was reversed (Scheme 122). 

Independent of the nature of the respective solid electroactive crystal, it is a main feature of these systems that the electron transfer takes place at the three-phase boundary microcrystal electrode electrolyte, and the (frequently even electrochemically reversible) electron transfer is accompanied by the transfer of cations or anions between the microcrystal and the electrolyte phase, in order to maintain electroneutrality. This situation of a three-phase electrode, where the immobilized electroactive solid phase is simultaneously in contact with an electron-conducting phase (e.g., a metal or graphite) and also with an electrolyte solution phase, is illustrated in Figure 6.1. 

The conditions required to favor esterification can be obtained in different manners. It is possible to add a water-miscible solvent that will lower the water concentration and increase the solubility of organic substrates and products. It is also possible to work in a two-phase system with a non-water-miscible solvent, which will serve as a reservoir for the substrates and products. This can be achieved either with macroscopic phases or with highly dispersed systems such as reversed micelles. In the above-mentioned cases, the enzyme-catalyzed reaction takes place in the aqueous phase or at the phase interface. The enzyme can be dissolved in this phase or immobilized by covalent attachment to a solid carrier... 

The results described herewith demonstrate that the activity of Ru metathesis catalysts can be enhanced by introduction of EWGs without detriment to catalysts stability. This principle can be used not only to increase the catalyst activity, but also to alter its physical-chemical properties, such as solubility in given medium or affinity to silica gel. An example of novel immobilization strategy, based on this concept is presented. In fact, the possibility of reversibly binding catalysts to a solid phase is of major importance for industrial applications, particularly when continuous flow processes with immobilised homogeneous catalysts are pursued. 

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