1.2.3- triazole linker

A. Dondoni and A. Marra, C-glycoside clustering on calix[4]arene, adamantane, and benzene scaffolds through 1, 2, 3-triazole linkers, J. Org. Chem., 71 (2006) 7546-7557. 

In addition, a new functional polymer in which proline was bonded to polystyrene through a 1,2,3-triazole linker was apphed to the asymmetric aldolisation of cyclohexanone with benzaldehydes in water. The use of this resin allowed the combination of excellent yields, diastereo- and enantioselec-tivities to be recorded in all the studied cases, as shown in Scheme 2.9. 

A 1,2,3-triazole-based solid-phase click linker was developed with an aldehyde functionality or a regenerative Michael acceptor (REM) functionality (Figure 11.1). In addition, a chiral pyrrolidine catalyst was grafted to the resin with a 1,2,3-triazole linker, enabling enantioselective Michael addition of ketones to nitroolefins... 

Figure 11.2. Polymer-supported chiral catalyst with a 1,2,3-triazole linker.

Figure 21 A schematic of the rotaxanes made by Fort et al., with the blue ovals representing lactose nnits, the red trnncated cones representing a-cyclodextrin, and the yellow pentagons representing the triazole linkers.

Recently, a Click polymerization strategy has been utilized to produce glycopolymers in which carbohydrates are incorporated into the backbone [198, 199]. Eissa and Khosravi demonstrated the copper wire-catalyzed Click polymerization of di-alkyne-terminated PEG with di-azide-functionalized trehalose prepared by tosylation/acetylation of a,a-D-trehalose followed by azidation reaction (Scheme 12) [199]. The produced alternating linear glycopolymers with triazole linkers were fully characterized and the polymer with a PEG segment of 600 gmol showed a lower critical solution temperature (LCST) at 39°C, which is known as the fever temperature. This material constituted a new class of temperature-responsive water-soluble glycopolymers. 

Kumar et reported the synthesis of pyrene-modified nucleotides and their effects in secondary nucleic acid structures. Pyrene was attached to the 5 -position of thymidine (26a) or to the 2 -position of 2 -deojgairidine via a triazolomethylene linker (26b), or via a triazole linker (26c). These nucleosides were converted into their phosphoramidites and then incorporated into oligonucleotides, and analysed by thermal stability and fluorescence studies. These experiments indicated that these oligonucleotides can act as specific recognition probes. 

Figure 17.3 Maleimide-modified glass slides (1) can be derivatized using two chemoselective ligation reactions to create biotin modifications. In the first step, alkyne-PEG4-cyclopentadiene linkers (2) are added to the maleimide groups using a Diels-Alder reaction. In the second reaction, an azido-PEG4-biotin compound (3) is reacted with the terminal alkyne on the slide using click chemistry to result in another cycloaddition product, a triazole ring.

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. 

Merrifleld 1,2,3-triazole resins 183 and 184 were prepared and utilized in the BAL (Backbone Amide Linker) strategy to synthesize amides 185 via sequential reductive aminations, amide couplings, and traceless resin cleavage with trifluoroacetic acid <03OL1753>. 

Oxalyl-CPG is obtained by reacting oxalyl chloride and 1,2,4-triazole with a 3 -hydroxyl nucleoside and LCAA-CPG. Cleavage of the oxalyl linker can be effected by a variety of mild reagents including triethylamine, propylamine-DCM, 5% ammonium hydroxide in methanol, or 0.5 M cesium fluoride in methanol for 15 min. Alternatively, 0.5 M DBU in either pyridine, dichloromethane, or dioxane was shown to effect full cleavage of the oxalyl linkage in less than 30 min at room temperature [111]. 

Based on an aminoalkylurethane linker attached to the Wang resin 155, Zaragoza et al. developed a solid-phase synthesis of 1,2,3-triazoles. Thus, as shown in Scheme 4.1.30, Wang resin 84 was primarily treated with 4-nitrophenyl chloroformate 153 in the presence of pyridine to give 154 and then reacted with piperazine in DMF to produce 155. Subsequent reaction with a freshly prepared solution of 3-oxobutyric acid phenyl ester afforded resin-bound 3-oxobutyryl piperazine 156. In the presence of triethylorthoformate, the condensation of 156 with primary aliphatic amines readily produced the corresponding 3-amino-2-butenoic acid amides attached to the solid support (157). 

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