Solid supports Tentagel

The first solid-phase application of the Ugi four-component condensation, generating an 18-member acylamino amide library, was presented in 1999 by Nielsen and Hoel [53]. The authors described a library generation utilizing amino-functionalized PEG-polystyrene (Tentagel S RAM) as the solid support (Scheme 7.36). A set of three aldehydes, three carboxylic acids, and two isonitriles was used for the generation of the 18-member library. 

The same authors performed a microwave assisted Stille reaction on the Rink amide (RAM) Tentagel polymer-tethered 4-iodobenzoic acid [5 b]. Successful palladium-catalyzed coupling of heteroaryl boronic acid with anchored 4-iodobenzoic acid enabled both >99% conversion of the starting material within 3.8 min (45 W) and a minimal decomposition of the solid support. The coupling reactions were realized in a mixture of polar solvents (H20-EtOH-DME, 2.5 1.5 6). 

Interestingly, the Suzuki reaction worked smoothly on solid supports and high yields of a variety of products were reported under these reaction conditions (Eq. 11.22) [36]. 4-Bromo- and 4-iodobenzoic acid linked to Rink-amide TentaGel re-... 

The coupling and cycloaddition could also be achieved as a one-pot procedure on a polymer support, as shown in Eq. (11.34), in which a Rink linker on TentaGel was used. Negligible decomposition of the solid support was reported [50]. 

Another metal-catalyzed microwave-assisted transformation performed on a polymer support involves the asymmetric allylic malonate alkylation reaction shown in Scheme 12.4. The rapid molybdenum(0)-catalyzed process involving thermostable chiral ligands proceeded with 99% ee on a solid support. When TentaGel was used as as support, however, the yields after cleavage were low (8-34%) compared with the corresponding solution phase microwave-assisted process (monomode cavity) which generally proceeded in high yields (>85%) [30],... 

Table 9.1 shows the method s versatility across several solid-support types. Care must be taken to dry the tentagel resins by lyophilization for 24 h before subjecting them to the reaction conditions. In the examples shown, quantitative conversions were obtained as determined by elemental analysis and 13C NMR. The mild reaction conditions are most evident by the quantitative conversion of SASRIN resin to its corresponding chloromethyl... 

PEG has been converted into a solid support by grafting functionalized polyethylene glycol chains onto polystyrene to form constructs such as TentaGel ... 

Scheme 19 Synthesis of thiol containing 2,5-DKP s for use in MMP inhibition. Solid support was done using TentaGel S OH or ArgoGel-OH. (Trt = triphenyhnethyl, TES = triethylsilane). Two representative 3D conformations of 119A (blue) and 119B (cyan). Yield shown represents yield over all steps...

Multi-component reactions where three or more components build a single product have received considerable interest for several years. Since most of these reactions tolerate a wide range of building block combinations, these types of reactions are frequently applied for combinatorial purposes. A solid-phase application towards the Ugi four component condensation (Ugi-4CC) generating a 18-member acylamino amide library appeared in 199939. The acylamino amide library was synthesised using amino-functionalised PEG-polystyrene (TentaGel S RAM) as the solid support. (Scheme 7.22). 

An example of catalysts which are themselves heterogeneous are the poly-amino acids used for the asymmetric Julia-Colonna-type epoxidation of chalcones using alkaline hydrogen peroxide (Section 10.2) [8]. Because of the highly efficient synthesis of epoxides, this process also has attracted industrial interest (Section 14.3). Since recent work by the Berkessel group revealed that as few as five L-Leu residues are sufficient for epoxidation of chalcone, several solid-phase-bound short-chain peptides have been used, leading to enantioselectivity up to 98% ee [14], For example, (L-Leu)5 immobilized on TentaGel S NH2 , 8, was found to be a suitable solid-supported short-chain peptide catalyst for epoxidations. 

Furthermore, cyanation followed by a subsequent cycloaddition, forming a tetrazole, was implemented as a rapid one-pot procedure on TentaGel-support, as depicted in Scheme 18. Only an insignificant decay of the solid support was experienced under the high-temperature conditions applied. 

Because the labeled tetrapeptide does not bind to the unmodified solid support Amino-TentaGel, the observed fluorescence activity is not because of unspecific interaction with the solid support itself. 

Another venue for saccharide display is on solid support. Resins that have been employed include polystyrene beads, polystyrene modified with polyethylene glycol (TentaGel), and... 

Furthermore, the internal reflection spectra of these reactions are much less distorted by the absorption bands of the solid support than are the transmission spectra recorded from KBr pellets made of polystyrene or TentaGel beads. In Fig. 3 the spectra of polystyrene resin (upper curve) and of a polystyrene Mega Crown (lower curve), both loaded with adipinic acid monoamide, are shown. The disturbing polystyrene bands are marked P. ... 

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