Supports in solid-phase

Scheme 4.8 Use of trichloracetimidate donors of polystyrene supports in solid-phase oligosaccharide synthesis.

Scheme 4.12 Application of CPG support in solid-phase oligosaccharide synthesis using glycosyl trichloroacetimidates.

Rasoul, F., Ercole, F., Pham, Y., et al. (2000) Grafted supports in solid-phase synthesis. Biopolymers (Pept. Sci.) 55, 207-216. 

Structural analysis of linear polymers molecularly dissolved in a suitable solvent using and solution phase NMR spectroscopy is long established [87-89]. Not surprisingly therefore when a linear soluble polymer is used as a support in solid phase synthesis and solution phase NMR spectroscopy can be a powerful tool in following the chemical synthesis on the support [90]. Figure 15.3.58, for example, shows a series of H NMR spectra of dissolved linear polymer samples taken at various stages in the solid phase synthesis of oligoethers on soluble polystyrene [91]. The various chemical steps Fig. 15.3.59 are clearly demonstrated. 

Role of polymeric support in solid-phase peptide synthesis... 

Although a number of issues are correlated with the use of this material, gel-type polystyrene resins are the most used supports in solid-phase chemistry, because of their acceptable loading capacity and relative good kinetics when fully swollen in good solvents. 

Although gel-type resins are the most widely used supports in solid-phase chemistry, it has been found that such supports are not always the most suitable for peptide synthesis. This is due to two main factors polystyrene chains are hydrophobic and are not completely compatible with peptides and, furthermore, bulky peptides can adopt unfavorable conformations within the polystyrene cross-linked matrix. 

Polyamide support in solid-phase synthesis 16, 424s31 ... 

Piel970 Pietta, P.G. and Marshall, G.M., Amide Protection and Amide Supports in Solid-Phase Peptide Synthesis, J. Chem. Soc., Chem. Commun., (1970) 650-651. 

Use of CNBr to cleave peptides from the polymer support in solid-phase peptide synthesis (55-98% yields). 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information for this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful... 

Gels made in this way have virtually no usable porosity and are called Jordi solid bead packings. They can be used in the production of low surface area reverse phase packings for fast protein analysis and in the manufacture of hydrodynamic volume columns as well as solid supports for solid-phase syntheses reactions. An example of a hydrodynamic volume column separation is shown in Fig. 13.2 and its calibration plot is shown in Fig. 13.3. The major advantage of this type of column is its ability to resolve very high molecular weight polymer samples successfully. 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information on this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful list, with references, of many protected amino acids (e.g., -NH2, COOH, and side-chain-protected compounds) has been compiled/ Some general methods for the preparation of esters are provided at the beginning of this chapter conditions that are unique to a protective group are described with that group/ Some esters that have been used as protective groups are included in Reactivity Chart 6. 

Kobayashi S, Aoki Y. />-Benzyloxybenzylamine (BOBA) resin. A new polymer-supported amine used in solid-phase organic synthesis. Tetrahedron Lett 1998 39 7345-7348. 

Hu Y, Porco JA, Jr, Labadie JW, Gooding OW, Trost BM. Novel polymer-supported trialkylsilanes and their use in solid-phase organic synthesis. J Org Chem 1998 63 4518 1521. 

However, other polymer composite materials also popular in solid-phase synthesis, such as polyethylene or polypropylene tea bags , lanterns, crowns, or plugs, are generally less suitable for high-temperature reactions (>160 °C). Therefore, micro-wave irradiation is typically not a very suitable tool to speed up reactions that utilize these materials as either a solid support or as containment for the solid support. 

Bis(indolyl)nitroethanes are obtained readily in 7-10 min in high yields (70-86%) on fine TLC-grade silica gel (5-40 pm) by Michael reaction of 3-(2 -nitrovinyl) indole with indoles. The same reaction reported requires 8-14 h for completion at room temperature [77]. Several functionalized resins have been prepared from Merrifield resin via a MW-assisted procedure that utilized mixed solvent system to facilitate the swelling of resins and coupling with microwaves [78], These resins can function as solid supports or polymeric scavengers in solid phase synthesis. 

After isolating the product of a solid phase synthesis, the support (resin + linker) is usually discarded as waste, although successful examples of its reuse in further synthetic cycles are known with trityl type linkers (Frechet and Haque 1975). To reduce both volume of operation and amount of waste, the loading of the resin (quantified as millimoles of functionality per gram) has to be increased. Besides theoretical limitations (for polystyrene this is reached when every phenyl ring is substituted by the linker), there may be practical boundaries for using highly loaded resins in solid-phase supported synthesis. This issue was studied... 

A van Vliet, RH Smulders, BH Rietman, GI Tesser. Protected peptide intermediates using a trityl linker on a solid support, in R Epton, ed. Innovations and Perspectives in Solid Phase Synthesis. Proceedings of the 2nd Symposium. Intercept, Andover,... 

E Atherton, V Wooley, RC Sheppard. Internal association in solid phase peptide synthesis. Synthesis of cytochrome C residues 66-104 on polyamide supports, (trif-luoroacetyl) J Chem Soc Chem Commun 970, 1980. 

Once it is part of a cyclic dipeptide, the prolyl residue becomes susceptible to enantiomerization by base (see Section 7.22). The implication of the tendency of dipeptide esters to form piperazine-2,5-diones is that their amino groups cannot be left unprotonated for any length of time. The problem arises during neutralization after acidolysis of a Boc-dipeptide ester and after removal of an Fmoc group from an Fmoc-dipeptide ester by piperidine or other secondary amine. The problem is so severe with proline that a synthesis involving deprotection of Fmoc-Lys(Z)-Pro-OBzl produced only the cyclic dipeptide and no linear tripeptide. The problem surfaces in solid-phase synthesis after incorporation of the second residue of a chain that is bound to the support by a benzyl-ester type linkage. There is also the added difficulty that hydroxymethyl groups are liberated, and they can be the source of other side reactions. 

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