Solid Phase Organic Synthesis SPOS

At the time of writing this book, SPOS is in an area of relative infancy but has considerable potential. One of the main difficulties in SPOS lies in the lack of techniques available to monitor reactions carried out on polymer supports. Unlike reactions in solution phase, reactions on solid support cannot be monitored with relative ease and this has hindered the progress as well as the efficacy of solid supported synthesis of small non-peptidic molecules. Despite these difficulties, a large body of studies is available for SPOS. Recent reviews incorporate 

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In the 1990s the technique of solid-phase organic synthesis (SPOS) became generally popular, but especially in the medicinal chemistry community, for lead detection and lead optimization via combinatorial techniques. The combination with microwave irradiation brought an elegant solution for the problem of the notoriously slower reactions compared to those in solution phase. 

Photolabile linkers play an important role in solid-phase organic synthesis (SPOS) due to their stability under both acidic and basic conditions. The ONb photolabile linker was modified to improve cleavage rates and yields Fmoc-Tos-OFI was released in 87% yield after 23 h (Scheme 4) [24]. Specifically, the primary alcohol was changed to a secondary benzylic alcohol and the attachment to the resin was through an alkyl chain as opposed to an amide function. Linker 20 was used for the production of carboxylic acids or carbohydrates. A second example... 

One of the key technologies used in combinatorial chemistry is solid-phase organic synthesis (SPOS) [2], originally developed by Merrifield in 1963 for the synthesis of peptides [3]. In SPOS, a molecule (scaffold) is attached to a solid support, for example a polymer resin (Fig. 7.1). In general, resins are insoluble base polymers with a linker molecule attached. Often, spacers are included to reduce steric hindrance by the bulk of the resin. Linkers, on the other hand, are functional moieties, which allow the attachment and cleavage of scaffolds under controlled conditions. Subsequent chemistry is then carried out on the molecule attached to the support until, at the end of the often multistep synthesis, the desired molecule is released from the support. 

Solid-phase organic synthesis (SPOS) exhibits several shortcomings, due to the nature of the heterogeneous reaction conditions. Nonlinear kinetic behavior, slow reactions, solvation problems, and degradation of the polymer support due to the long reaction times are some of the problems typically experienced in SPOS [2], Any technique which is able to address these issues and to speed up the process of solid-... 

Other microwave-assisted parallel processes, for example, involving solid-phase organic synthesis (SPOS) have already been discussed in Sect. 12.2. (Schs. 12.6, 12.7, and 12.10). In the majority of cases described so far, however, domestic multimode microwave ovens have been used as heating devices, without utilizing specialized reactor equipment. Since reactions in household multimode ovens are notoriously difficult to reproduce due to the lack of temperature and pressure control, pulsed irra-... 

Beaver, K. A. Siegmund, A. C. Spear, K. L. Application of the Sulfonamide Functional Group as an Anchor for Solid Phase Organic Synthesis (SPOS), Tetrahedron Lett. 1996,37, 1145-1148. 

Solid-phase organic synthesis (SPOS) is an established technique for generation of peptides,12 nucleotides,3 and more recently, carbohydrates (oligosaccharides).4-5 Supported syntheses of nonbiological oligomers6 16 and other small molecules17 21 have also been reported, reflecting the method s... 

During the early part of this decade, most efforts in high-throughput synthesis utilized solid phase organic synthesis (SPOS) techniques.1-3 SPOS was a natural outgrowth of earlier methods used to synthesize peptides and oligonucleotides.4 This method has several advantages over traditional solution-phase synthesis ... 

Notwithstanding the reduced reaction times and improved yields, the need to use column chromatography to purify the target 1,4-DHP encumbers the application of the procedure for the fast preparation of screening libraries. To address the purification issue, various phase-separation techniques could be employed, such as solid-phase organic synthesis (SPOS). 

However, it was not until Merrifield developed a polystyrene matrix for peptide synthesis that a broad range of functionalized solid supports became available [91], leading to solid phase organic synthesis (SPOS) and eventually to polymer-assisted solution synthesis (PASS). Both of these techniques are heavily utilized by industry, especially for rapid library synthesis. 

Solid-phase organic synthesis (SPOS) has been revolutionary in the quest to produce libraries of structurally diverse molecules both quickly and cheaply. The utility of benzyl and aryl vinyl sulfones in the traceless linker synthesis of amines... 

Linkers for Solid-Phase Organic Synthesis (SPOS) and Combinatorial Approaches on Solid Supports... 

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