Solid supports polystyrene

A method in which the C-terminal amino acid is attached to a solid support (polystyrene beads) and the peptide is synthesized in the C —> N direction by successive coupling of protected amino acids. When the peptide is complete, it is cleaved from the solid support, (p. 1185)... 

Another important feature of the synthesis of oligonucleotide-peptide conjugates is the choice of a solid support. Polystyrene supports are used in peptide synthesis and CPG supports are incorporated for oligonucleotide synthesis. Most reports describe the use of CPG for the synthesis of oligonucleotide-peptide conjugates [13,14,26,27,36,63,74]. However, in some cases low coupling yields have been reported with CPG and alternative supports have been described, such as Teflon [34], polystyrene (PS)... 

Combinatorial chemistry has significantly increased the nurnjjers of molecules that can be synthesised in a modern chemical laboratory. The classic approach to combinatorial synthesis involves the use of a solid support (e.g. polystyrene beads) together with a scheme called split-mix. Solid-phase chemistry is particularly appealing because it permits excess reagent to be used, so ensuring that the reaction proceeds to completion. The excess... 

For quantitative analysis of solid supported thiol residues on free macroporous or PEG grafts, Ellman s reagent has been used [5,5 -dithio-hfr-(2-nitrobenzoic acid]. However only qualitative information can be gained using lightly crosslinked polystyrene resins [Badyal et al. Tetrahedron Lett 42 8531 2007]. 

The Pictet-Spengler reaction has been carried out on various solid support materials " and with microwave irradiation activation.Diverse structural analogues of (-)-Saframycin A have been prepared by carrying out the Pictet-Spengler isoquinoline synthesis on substrates attached to a polystyrene support. Amine 20 was condensed with aldehyde 21 followed by cyclization to give predominantly the cis isomer tetrahydroisoquinoline 22 which was further elaborated to (-)-Saframycin A analogues. 

Amine bound to a Wang-polystyrene resin 381 was acylated with 4-oxo-4Ff-pyrido[l,2-u]pyrazine-3-carboxylic acid in the presence of bromotrispyrrolidinophosphonium hexafluorophosphate and /-Pr2NEt in A-methylpyrrolidone (98MIP16). l-(4-Cyclohexyl-4-r / r-butylaminocarbo-nyl-l-piperidyl)-2-(4-fluorophenyl)ethylamine was acylated with perhydro-pyrido[l,2-u]pyrazine-3-carboxylic acid (01MIP19). An amino group of a macrocyclic compound attached to a solid support was acylated with... 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

In place of N-methylimidazole (Melm), only dimethylaminopyridine (DMAP) could be substituted. The solid-supported amines piperidinomethyl- or morpholinomethyl polystyrene resins, pyridine, and tertiary amines like triethylamine andN-methylmorpholine were not effective. 

As for the solid support, several polymer-supported amines were tested (Fig. 2). For either the pyrazole and isoxazole synthesis, the best results were given by aniline-functionalized cellulose, which has also the advantage of a relatively low cost. For the 2-aminopyrimidine library, polystyrene-based piperazine and piperidine gave products with a much higher purity compared with other secondary non-cyclic or primary amines, hi both cases, the resins could be reused for up to four times before degradation in their behavior was observed. This reusability could be further enhanced (up to 10 cycles for cellulose-based aniline) when the microwave-assisted protocols were used. 

The first solid-phase application of the Ugi four-component condensation, generating an 18-member acylamino amide library, was presented in 1999 by Nielsen and Hoel [53]. The authors described a library generation utilizing amino-functionalized PEG-polystyrene (Tentagel S RAM) as the solid support (Scheme 7.36). A set of three aldehydes, three carboxylic acids, and two isonitriles was used for the generation of the 18-member library. 

Similarly, a solid-supported imide has been reported to serve as an acylating reagent under microwave conditions by Nicewonger and coworkers [130], The starting imide was immobilized on aminomethyl polystyrene and in this case benzoyl chloride was chosen to prepare the acylating reagent (Scheme 7.111). Primary amines and piperazines were smoothly acylated at room temperature, but more hindered secondary amines required more time and higher temperatures, and anilines... 

Abstract. The direct scale-up of a solid-phase synthesis has been demonstrated with 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide and an arylsulfonamido-substituted hydroxamic acid derivative as examples. These compounds were obtained through combinatorial chemistry and solution-phase synthesis was used in parallel to provide a comparison. By applying highly loaded polystyrene-derived resins as the solid support, a good ratio between the product and the starting resin is achieved. We have demonstrated that the synthesis can be scaled up directly on the solid support, successfully providing the desired compounds easily and quickly in sufficient quantities for early development demands. 

Immobilized catalysts on solid supports inherently have benefits because of their easy separation from the products and the possibility of recycling. They are also expected to be useful for combinatorial chemistry and high-throughput experimentation. The polystyrene-bound BINAP/DPEN-Ru complex (beads) in the presence of (CH3)3COK catalyzes the hydrogenation of l -acetonaphthone with an SCR of 12 300 in a 2-propanol-DMF mixture (1 1, v/v) to afford the chiral alcohol in 97% ee (Fig. 32.35) [113]. This supported complex is separable... 

PEG has been converted into a solid support by grafting functionalized polyethylene glycol chains onto polystyrene to form constructs such as TentaGel ... 

FIGURE 5.2 Synthesis of a peptide on a solid support according to Merrifield in 1964. PS = polystyrene. Initially, the protector was benzyloxycarbonyl, removed by HBr in CHjCOjH, followed by final deprotection with the same reagent at 78°C. The current protocol employs CF3C02H and HF, respectively. 

Parallel Synthesis We start the reaction by using two sets of building blocks, amines (A) and carboxylic acids (B). The amines are first attached to solid supports, normally polystyrene beads coated with linking groups, in separate reaction vessels for each amine. After the amines have been attached, excess unreacted amines are washed off. Next, the carboxylic acids are added to the amines to form the desired amides. We illustrate these steps in Fig. 3.8. Assuming there are 8 amines to react with 12 carboxylic acids in a 96-well plate with 8 rows and 12 columns of tiny wells, the amines, A1 to A8, are added across the rows to each well containing the polystyrene beads. Different types of carboxylic acids, B1 to B12, are added to the wells in each column. 

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