Functionalized supports

PLCs are classified by the number of the I/O functions supported. There are several sizes available, with the smallest PLCs supporting less than 128 I/O channels and the largest supporting over 1023 I/O channels. I/O modules are available that support high-current motor loads, general-purpose voltage and current loads, discrete inputs, ana-... 

In the next step, the best candidate from the series 2-oxo-4-(9-phenanthryl)-dihy-dropyrimidine 22 was prepared and isolated in enantiomerically pure form, then attached to a macroporous polymer support. To attach the isolated selector to the amino functionalized macroporous polymethacrylate support, a suitable reactive handle had to be introduced into the dihydropyrimidine. We chose to functionalize the methyl group at the C6 carbon atom by a simple bromination to afford (-)-22. Coupling of this compound to the amino functionalized support then gave the desired chiral stationary phase CSP 12 (Scheme 3-6) containing 0.20 mmol g of the selector. 

A second strategy is to attach a linker (also referred to as a handle or anchor) to the resin followed by assembly of the molecule. A linker is bifunctional spacer that serves to link the initial synthetic unit to the support in two discrete steps (Fig. 3). To attach a linker to a chloromethyl-PS resin, a phenol functionality such as handle 4 is used to form an ether bond (Fig. 4). To attach the same handle to an amino-functionalized support, acetoxy function 5 or a longer methylene spacer of the corresponding phenol is applied to form an amide bond. Both of these resins perform similarly and only differ in their initial starting resin [4], An alternative approach is to prepare a preformed handle in which the first building block is prederivatized to the linker and this moiety is attached to the resin. For peptide synthesis, this practice is common for the preparation of C-terminal peptide acids in order to reduce the amount of racemization of the a-carbon at the anchoring position [5],... 

Functionalized supports with amino groups such as benzhydrylamine (BHA) 26 [32] and 4-methylbenzhydrylamine (MBHA) 3 [3] provided C-terminal amides upon HF cleavage (Fig. 2). Polyalkoxyaminobenzyl and alkoxydiphenylamino resins such as PAL (5-(4-aminomethyl-3,5-dime-... 

Importantly, 1 can be heterogenized on NH2-functionalized supports such as xerogels, fibers, etc., and in this form used repeatedly without significant loss of catalytic activity (Figure 2). The supported Ce-POM can be separated from the reaction mixture by simple filtration. 

Recently, a solid-phase synthesis was used iteratively for the synthesis of organic substances like oligocarbamates [13] and oligoureas [14] by repeated coupling to amino-functionalized supports. In this way substance libraries [15] have been developed showing that iterative methods can also be employed in combinatorial chemistry [16]. 

Furthermore, the use of silica-based ceramic matrices as functional supports has a number of practical, unique advantages including stability towards harsh conditions, low swelling and consistent binding sites... 

Support functions Support functions Support functions... 

Most conventional scavenging is based on the concept of complementary reactivity. In the simplest cases, electrophilic and nucleophilic species are sequestered via a reciprocally functionalized support (Scheme 2.11 see also Tab. 2.1) likewise, acids and bases can be removed via salt formation with a solid-supported base or acid. 

In the 1970s and 1980s, however, it was believed that the key to wider use of solid-phase supported reagents and catalysts is their adoption in industry for fine chemical and pharmaceutical manufacturing on a large scale. In fact, this restricted view hampered their wide use [7]. The dramatic developments in the need for compound library preparation in pharmaceutical and agrochemical industries have finally removed functionalized supports from their academic corner and helped reinvent them for industrial purposes and applications. 

Other functionalized supports that are able to serve in the asymmetric dihydroxylation of alkenes were reported by the groups of Sharpless (catalyst 25) [88], Sal-vadori (catalyst 26) [89-91] and Cmdden (catalyst 27) (Scheme 4.13) [92]. Commonly, the oxidations were carried out using K3Fe(CN)g as secondary oxidant in acetone/water or tert-butyl alcohol/water as solvents. For reasons of comparison, the dihydroxylation of trons-stilbene is depicted in Scheme 4.13. The polymeric catalysts could be reused but had to be regenerated after each experiment by treatment with small amounts of osmium tetroxide. A systematic study on the role of the polymeric support and the influence of the alkoxy or aryloxy group in the C-9 position of the immobilized cinchona alkaloids was conducted by Salvadori and coworkers [89-91]. Co-polymerization of a dihydroquinidine phthalazine derivative with hydroxyethylmethacrylate and ethylene glycol dimethacrylate afforded a functionalized polymer (26) with better swelling properties in polar solvents and hence improved performance in the dihydroxylation process [90]. 

Tethering approaches with Si(OEt)Me2 substituents on the ring, appropriate for both solid state sol-gel chemistry toward Zr-functionalized support and for solution chemistry toward analogous zirconium silsesquioxanes, exist [39]. 

ILs can be immobilized on a functionalized support which contains one component of the IL or a precursor to such a component. The IL may be immobilized via the anion by treating a support with an anion source, e.g., an inorganic halide, before the IL is applied or formed. Alternatively, the IL may be immobilized by having the cation covalently bound to the support, e.g., through silyl groups, or incorporated in the support by synthesizing the support in the presence of a suitable base. The immobilized ILs are of use as catalysts, for example for the Friedel-Crafts reaction. 

The number of basis functions involved in E+ or S+ symmetiy functions. The number of symmetry functions supported. 

After the patient has been asymptomatic for a period of approximately 6-12 months (continuation phase), the clinician has to decide who should receive maintenance therapy, which therapy to use, and for how long. The main goal of the maintenance phase is to prevent recurrences. This phase may last from 1 year to much longer, and is typically conducted at a visit frequency of every 1 to 3 months, depending on the patient s clinical status, functioning, support systems, environmental stressors, and motivation for treatment, and the existence of other psychiatric or medical disorders (Fig. 36.4). 

Buchmeiser, M. R. Metathesis Polymerization A Versatile Tool for the Synthesis of Surface-functionalized Supports and Monolithic... 

In the same way, dipyridyl amide-functionalized supports suitable for the SPE of metal ions from aqueous solutions can be prepared. The resins are synthesized via the copolymerization of the functional monomer endo-norbornene-5-yl-N,N-di-2-pyridyl carboxylic amide with a molybdenum-based catalyst (42). Essentially no loss of performance was observed after extensive use over more than twenty cycles. After exposure to air for at least 2 months, a change in color from bright white to yellow was observed. However, this change in color did not influence the characteristic properties of the resins. 

M.R. Buchmeiser and F.M. Sinner, Functionalized supporting materials which can be obtained by means of metathesis graft polymerization, WO Patent 0061288, assigned to Merck Patent Gmbh (DE) Buchmeiser Michael Rudolf (AT) Sinner Frank Michael (AT), October 19, 2000. 

V,/V -bis(acryIoyI)-l,3-diaminopropane. Amine deprotection after polymerization leads directly to the functionalized support. 

For some applications it might be desirable to cleave the product from a support in two or more portions. This can be realized by derivatizing a functionalized support with a mixture of different linkers that enable a sequential cleavage [9]. The resulting support can, for instance, be used to prepare and screen combinatorial peptide libraries by the mix-and-split method ([10-12] one different peptide on each bead). The first portion of peptide released would be tested for biological activity, and, once an active peptide had been identified, the remaining peptide on the support could be used for structure elucidation. 

A flexible means of access to functionalized supports for solid-phase synthesis is based on metallated, cross-linked polystyrene, which reacts smoothly with a wide range of electrophiles. Cross-linked polystyrene can be lithiated directly by treatment with n-butyllithium and TMEDA in cyclohexane at 60-70 °C [1-3] to yield a product containing mainly meta- and para-Iithiated phenyl groups [4], Metallation of noncross-linked polystyrene with potassium ferf-amylate/3-(lithiomethyl)heptane has also been reported [5], The latter type of base can, unlike butyllithium/TMEDA [6], also lead to benzylic metallation [7]. The C-Iithiation of more acidic arenes or heteroar-enes, such as imidazoles [8], thiophenes [9], and furans [9], has also been performed on insoluble supports (Figure 4.1). These reactions proceed, like those in solution, with high regioselectivity. 

C-Alkylations have been performed with both support-bound carbon nucleophiles and support-bound carbon electrophiles. Benzyl, allyl, and aryl halides or triflates have generally been used as the carbon electrophiles. Suitable carbon nucleophiles are boranes, organozinc and organomagnesium compounds. C-Alkylations have also been accomplished by the addition of radicals to alkenes. Polystyrene can also be alkylated under harsh conditions, e.g. by Friedel-Crafts alkylation [11-16] in the presence of strong acids. This type of reaction is incompatible with most linkers and is generally only suitable for the preparation of functionalized supports. Few examples have been reported of the preparation of alkanes by C-C bond formation on solid phase, and general methodologies for such preparations are still scarce. 

Vinylpolystyrene, a useful intermediate for the preparation of various functionalized supports for solid-phase synthesis [7,57-59], has been prepared by the polymerization of divinylbenzene [7], by Wittig reaction of a Merrifield resin derived phosphonium salt with formaldehyde [59-62], or, most conveniently, by treatment of Merrifield resin with trimethylsulfonium iodide and a base [63] (Figure 5.7). 

Thioglycosides have been prepared on solid phase by glycosylation of thiols with various types of glycosyl donor. Carbohydrate-derived thioethers have been used either to link carbohydrates to thiol-functionalized supports [9,26,78,79] or as glycosyl donors for the preparation of glycosides on solid phase (see Section 16.3.3). 

Covalent Attachment The covalent attachment of enzyme molecules via nonessential amino acid residues (that is, amino acids minus water) to water-insoluble, functionalized supports are the most widely used method for immobilizing enzymes. Functional groups of the nonessential amino acid residues that are suitable for the immobilization process are free a-, /3-, or y-carboxyl groups, a- or /3-amino groups, and phenyl, hydroxyl, sulfhydryl, or imidazole groups.2... 

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