Solid-phase synthesis specific compounds

Numerous resin supports are commercially available for solid-phase synthesis and some allow the acquisition of quite reasonable quality spectra of compounds bonded to them - and some don t. The resins to avoid (if you intend trying to monitor your reactions by MAS-NMR) are any that are based purely on cross-linked polystyrene. These are too rigid and afford little or no mobility to any bound compound. These resins are relatively cheap and have high specific loadings but will give very poor spectra even in a MAS probe. We see little point in running spectra of compounds on these resins as the quality of the spectra make them virtually useless - and perhaps worse - potentially misleading. 

The requirement for diverse compound libraries by means of solid-phase synthesis led to the development of hnkers for most functional groups found in organic synthesis. The number of hnkers developed for a specific group also reflects the distribution of pharmacophoric groups present in natural products and other bioactive compounds. Tab. 3.16 gives an overview of examples of hnkers for different functional groups. 

As in solid-phase synthesis programs, one of the most challenging problems with solution-phase synthesis is to separate products obtained in the reaction mixtures and identify the compound or compounds with biological potency or some other desirable property. An especially effective technique that has been developed to deal with this problem is called indexed libraries, also known as orthogonal libraries. In this process, each product compound is prepared twice. Analysis then permits identification of the positive part of the compound and the negative part of the compound with the greatest potency. Once these have been determined, it is possible to identify the specific compound most active in the mixture. 

The first part of the chapter covers several examples of stereoselective solution and solid-phase approaches to obtaining natural product analogs. The examples discussed here represent focused strategies to library generation that are based on specific bioactive natural products. These libraries have often served as natural product analogs in searches for better biological responses than those exhibited by the parent natural products. The generation of libraries of natural product-like compounds by solution and solid-phase synthesis methods is discussed in the second half. 

Nanocrystalline one-domain magnetite (fraction of 20—50 nm) was obtained also by the method of solid phase synthesis in the inert atmosphere. As initial compounds, metal-organic compounds of bi- and trivalent iron were used. Magnetite obtained by the solid phase method showed the highest values of coercive force (150—240 Oe), with the specific surface of 40 m /g. 

Unlike OS, solid-phase methods will virtually always be invented for application in combinatorial organic synthesis. To meet these specific needs, SPOS procedures will focus not on multistep reactions leading to a desired final compound but rather on a single type of synthetic transformation accomplished on... 

Solid-phase peptide synthesis offers a fast and convenient route for many peptides when isotope-enriched compounds are not required. Classical synthesis additionally permits the use of non-natural amino acids and allows site-specific isotope labeling. Although Fmoc protected 15N-labeled amino adds are commercially available, the cost of such synthesis is usually prohibitive, and the peptides from chemical synthesis require perdeuterated detergents and unfortunately exclude investigation of internal dynamics through measurement of 15N relaxation. 

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