Solid supports Argogel

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...

The reaction of an a-haloketone with thiourea gives rise to the 2-aminothiazole. This reaction has been used in a combinatorial approach for the synthesis of libraries of 2-aminothiazoles in excellent yields and purities first in the solution phase <1996BML1409> and then on a solid support using Rink amide MBHA, glycyl-Rink amide MBHA, and reductively aminated ArgoGel MB-CHO resins (Scheme 55) <1998JOG196>. 

In 1998, Dankwardt used for the first time ester linkers for the synthesis of hydroxamates [116]. The synthesis of hydroxamates and hydroxamic acids is a known synthesis on solid supports but former approaches used special hydroxamate linkers that had to be synthesized in previous reactions. The methodology published by Dankwardt is very simple because ArgoGel-OH resins can be used without further derivatization to bind protected amino acids 88 in the presence of coupling reagents. Hydroxamic acids 90 were cleaved by the addition of hydroxylamine in 21% (sterically hindered amino acids) to quantitative yields (glycin. Scheme 12). 

In another example, a polymer-supported chromium porphyrin complex was supported on ArgoGel Cl and then employed for the ring-opening polymerization of 1,2-cyclohexene oxide and C02 [95], This complex showed higher activity than a C02-soluble equivalent, and the solid nature of the catalyst meant that recycling of the catalyst was much easier. 

At present, two major families of supports are used for SPPS. Polystyrene, lightly cross-linked (e.g., 1%) with divinylbenzene, was used in most of Merrifield s seminal work and is still very popular for SPPS and solid-phase organic synthesis [1,22]. Polyethylene glycol (PEG) grafted onto polystyrene has found widespread application. The PEG chain can either be covalently attached to the polystyrene support (PEG-PS) [23-25] or ethylene oxide polymerized onto the polystyrene (Tentagel and ArgoGel) [26,27]. 

Advancements in solid-phase reactions have been facilitated by the introduction of HR-MAS NMR. The technique provides a powerful way to monitor and characterize compounds attached to resins, with a resolution comparable to solution-like spectra. An example of similar quality of NMR spectra obtained for a supported molecule by gel-phase HR-MAS NMR and for the same unsupported molecule in solution has been carried out in our group (Figure 4.3). This molecule is the methyl ester in solution phase, while it is the Argogel ester on solid phase. 

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