Solid-phase linkers Rink amide linker

Brown EG, Nuss JM. Alkylation of Rink s amide linker on polystyrene resin a reductive amination approach to modified amine-linkers for the solid phase synthesis of /Y-substiuited amide derivatives. Tetrahedron Lett 1997 38 8457-8460. 

Our library synthesis was carried out with a set of 27 tube-shaped solid phase synthesis support, called MicroTubes. These supports are prepared by radiation grafting of polystyrene ( — 350 pmol) onto polypropylene tubes, chemically functionalizing the polystyrene with aminomethyl groups to afford about 55 imol of amine per tube, inserting a reusable Rf ID tag into each tube, and heat-sealing the tube ends to prevent loss of the tag. The chemical conversion of all 36 aminomethyl tubes was carried out simultaneously using standard procedures with rink amide linker, each with —46 pmol of available amine per tube.1 2... 

Few preparations of nitriles have been performed on insoluble supports (Table 13.19). Aromatic and heteroaromatic nitriles have been prepared on solid phase from the corresponding iodoarenes by metallation followed by reaction with tosyl cyanide (Entry 1, Table 13.19). Moreover, the reaction of chloromethyl polystyrene with NaCN has been used to prepare support-bound benzyl cyanide (Entry 2, Table 13.19). Cleavage with simultaneous formation of nitriles can be achieved by treating polystyrene-bound sulfonylhydrazones with KCN (Entry 3, Table 13.19) or by cleaving amides from a Rink or Sieber linker with TFA anhydride (Entry 10, Table 3.38 [262]). Support-bound benzaldehydes have been converted into 3-aryl-2-propenenitriles by means of a Horner-Emmons reaction with (Et0)2P(0)CH2CN [263]. 

Peptoid dendrimers were synthesised using an Fmoc solid-phase strategy using a Rink amide linker and an aminomethyl-polystyrene resin and microwave-mediated DIC/HOBt chemistry (Fig. 25). The use of microwave heating allowed each... 

For this, the polystyrene resin bearing 3-bromobenzamide attached to the solid phase via a Rink amide linker was used. The 3-bromophenyl resin (75) (500 mg, 0.39 mmol), Pd(PPh3)2Cl2 (13.7 mg, 0.020 mmol), Cul (7.4 mg, 0.039 mmol), triphenylphosphine (20.5 mg, 0.078 mmol), the alkyne (28) (0.43 mmol), diethylamine (1.5 mL, 13.60 mmol), and DMF (0.5 mL) were stirred in a modified heavy-walled Smith Process Vial [200] at 120 °C for 25 min in the microwave cavity. The resin was then washed as follows ... 

Fmoc-protected 4-[(2 ,4 -dimethoxyphenyl)aminomethyl]phenoxymethyl resin (Rink amide resin) (5 g, 2.25 mmol) was subjected to repeated washes with 20% (v/v) piperidine/DMA until the UV absorption at 299 nm of the eluates reached baseline level. An additional five washes (50 mL) were carried out with pure DMA. Rink resin, bearing the amino group of the depro-tected linker, was acylated with a 0.3 m solution of a carboxyaldehyde (22.5 mL, 6.75 mmol) at rt (pre-activation for 40 min with 3.3 equiv. of DIG (7.23 mmol) and 3.3 equiv. of HOBt (7.23 mmol)) for at least 4 h, until a Kaiser test [81] was negative. The resulting solid-phase-grafted aldehydes 106 were utilized for the following derivatizations. 

Brol997a Brown, E.G. and Nuss, J.M., Alkylation of Rink s Amide Linker on Polystyrene Resin A Reductive Amination Approach to Modified Amine-Linkers for the Solid Phase Synthesis of N-Substituted Amide Derivatives, Tetrahedron Lett., 38 (1997) 8457-8460. 

Because of the origins of solid phase chemistry in peptide synthesis, amide formation is historically one of the most important reactions on solid supports. The most pubUc resins are the Rink amide linker 123 [146,147] and its derivatives that are formed by addition of the Knorr hnker [148] to polystyrene-derived resins. 

On the other hand, if the phosphopeptides are intended to be used in solution-phase assays, the synthesis can be carried out on a standard resin with common linkers. This includes the Rink amide or Wang-type linkers on polystyrene, TentaGel, or ChemMatrix supports. Upon completion of the peptide chain assembly, the peptides are released from the solid support by treatment with TFA-containing cocktails with concomitant removal of acid-labile side-chain protecting groups. Using these conditions robust protocols for rapid and efficient synthesis of phosphopeptides have been established. 

Fmoc-based solid-phase glycopeptide synthesis is compatible with the standard linkers (handles) widely used in peptide synthesis, such as Rink amide, Wang, SASRIN (mild acid cleavage), 2-chlorotrityl chloride (protected peptide acid), and Sieber (protected peptide amides). For combinatorial one-bead one-compound studies, both the safety-catch amide linker (SCAL, stable to both acid and base until sulfone reduction) [24] and the photocleavable linker 4-[4-(l-aminoethyl)-2-methoxy-5-nitrophenoxy] butyric acid [25 ] have been successfully applied. These linkers are suitable for displaying the frilly deprotected glycopeptides on bead while allowing their nondestructive recovery after bead assay. Concerning... 

It should be noted that the success of soHd phase Suzuki reactions can be dependant on the linker. In a study by Fernandez et al., optimal conditions for the Suzuki coupling of solid-supported 5-bromonicotinic acid with various boronic acids were found to vary for three different resins [126]. For amide resins, i.e.. Rink and BAL, aqueous base in a toluene/EtOH solvent gave high yields and purities for a range of boronic acids. However, for ester-bound Wang resin, anhydrous conditions were required to achieve good conversion over a wide variation in the aryl boronic acid. 

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