Linker indole

Contrary to an alkoxy benzene scaffold, secondary amides were generated via novel aldehyde linker 43 based upon an indole scaffold (Scheme 15) [52]. The indole resin was prepared from indole-3-carboxy-aldehyde in two steps and reacted with amines under reductive conditions to generate resin-bound secondary amines. Treatment of the resin with... 

More recently, Somfai and coworkers have reported on the efficient coupling of a set of carboxylic acids suitable as potential scaffolds for peptide synthesis to a polymer-bound hydrazide linker [24]. Indole-like scaffolds were selected for this small library synthesis as these structures are found in numerous natural products showing interesting activities. The best results were obtained using 2-(7-aza-l H-benzo-triazol-l-yl)-l,l,3,3-tetramethyluronium hexafluoride (HATU) and N,N-diisopropyl-ethylamine (DIEA) in N,N-dimethylformamide as a solvent. Heating the reaction mixtures at 180 °C for 10 min furnished the desired products in high yields (Scheme 7.4). In this application, no Fmoc protection of the indole nitrogen is required. 

For resin-bound carbamates (18-21), indole linker was the most acid-labile linker for this class of compounds. Rink linker ranked second. Resin (20) was cleaved with 0.5% TFA in 20 min. Resin (21) was cleaved with 1% TFA in 2 min. Resins (18) and (19) required higher concentration of TFA. Resin (18) was cleaved with 1% TFA in 5 h. Alternatively, resin (19) was cleaved with 1% TFA in 12 h and with 5% TFA in only 16 min (not shown). 

For resin-bound ureas (22-25), Indole and Rink linkers, generally ranked 1 and 2 in cleavage kinetics, were still the most acid-labile linker for this class of compounds. Resins (24) and (25) were cleaved with 0.5% TFA in 2 and 23 min, respectively. Resins (22) and (23) were cleaved with 1% TFA in more than 10 h. The order of cleavage rates is similar to carbamate compounds. 

Resin-bound sulfonamides (30-33) were easily cleaved by 1% TFA in 3 min or by 0.5% TFA in 2-7 h. Indole linker was still the most labile linker in this class of compounds. 

TFA). Among various linkers studied in this work, the indole linker [21] was found to be the most suitable linker in terms of cleavage kinetics and actual cost. Rink linker was the second best in term of kinetics. The rate of cleavage of various functional groups linked to the above-mentioned resins was as follows sul-fonamide>carbamate urea>amide. Results from this study demonstrated that optimization of cleavage conditions often led to more suitable conditions and safer release of precious compounds synthesized on a solid support. 

The iodination of cross-linked polystyrene has been achieved using iodine under strongly acidic reaction conditions [55] or in the presence of thallium(III) acetate [61], but this reaction does not proceed as smoothly as the bromination. More electron-rich arenes, such as thiophenes [45,62-64], furans [46], purines [65], indoles [66], or phenols [67,68] are readily halogenated, even in the presence of oxidant-labile linkers (Figure 6.2). Polystyrene-bound thiophenes have also been iodinated by lithiation with LDA followed by treatment with iodine [64],... 

Sandwich casting permits one to prepare an MIP film with uniform thickness [28, 106, 108, 109]. In this procedure, a drop of the solution containing a monomer, cross-linker, template and initiator is dispensed on the surface of a PZ transducer and covered with a microscope quartz slide. Then this assembly is exposed to UV light in order to initiate polymerization that results in a thin MIP film. The polymerization can be performed either on the activated immobilized initiator PZ transducer surface or on the bare transducer surface. For example, sialic acid has been determined with an MIP film immobilized on a platinum-film electrode of the quartz resonator using the former procedure [57]. That is, 1-butanethiol has been used for modification of the Pt surface. An indole-3-acetic acid plant hormone served as the template. An MIP-PZ chemosensor prepared that way operated reproducibly. That is, the coefficient of variation of the chemosensor performance was 9% for three different sensors. 

Another attractive method for E ring formation featured an intramolecular [2+3]cycloaddition of an azide moiety, emanating from the indole 3-position via a two-carbon linker, to, now, an electron-rich version of the C15-C16 double bond.19 The cycloaddition precursor 10 was made via 9, in turn assembled by regioselective cocylization of protected methoxyacetylene (Scheme 5). In a puzzling turn of events, thermolysis of the azide product in toluene at moderate temperature (to minimize nitrene formation) and in low concentration (to suppress intermolecular reactions) produced the two oxidized pentacyclic products 11 and 12 in a 2 1 ratio. Performing the reaction in a more polar solvent (DMF, 80 °C, 7 d) altered the ratio to 5 1.20... 

The use of dendrimers as soluble supports in combinatorial chemistry was recently introduced by Kim et al. [204] for the synthesis of a 27-member pool library of indoles (three pools by nine individuals). The structure of the dendritic support, which was prepared condensing the commercially available starburst polyamidoamine (PAMAM) dendrimer with the 4-hydroxymethyl benzoic acid (HMB) linker, is given in Figure 7.24. 

The indole linker 1.11 (68), easily prepared from aminomethyl PS resin and N-carboxyalkylated indole-3-carboxaldehyde, was used to support amines and to transform them on SP, obtaining, by release with TFA-DCM 1/1 in 30 min, a variety of compounds, including amides, sulfonamides, guanidines, ureas, and carbamates. 

The commercially available oxime linker 1.15 (72) has been used in peptide synthesis and for the SPS of small organic molecules such as indoles. Cleavage is carried out with either hydrazine (0.5 M hydrazine in CHCb-MeOH 2/1 for 10 min at rt) or with aliphatic amines or amino esters (DCM at rt for 12 h) to produce hydrazides and amides, respectively. 

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