Rink- acetic acid’-amide

Rink- acetic acid -amide, Knorr resin... 

In a subsequent paper on the use of the Stille reaction to form biaryls,58 the reaction was carried out under ambient conditions to allow robotic automation of the process. Attachment of the tin species to resin was very straightforward, in that 4-tri-n-butylstannylphenyl acetic acid was linked to Rink amide resin simply using a DIC coupling. Loading of this species was determined by tin elemental analysis and correlated with a quantitative ninhydrin test of free amines remaining on the support (Scheme 24). 

To Rink amide resin iieylated with. 1-iodobenzyloxy acetic acid (0.2 g, 0.094 mmol) were added DMA (4.7 mL), sodium acetate (23 mg, 0.28 mmol, 3 equiv.), B114NCI (56 mg, 0.20 mmol, 2 equiv.), and dimethyl itaconate (119 mg, 0.75 mmol,... 

The hydroxyl version of the Rink amide linker, known as the Rink acid resin (25), was developed as a tool for the preparation of protected peptide fragments [13]. The peptide-linker ester bond is labile to extremely weak acids, such as HOBt or acetic acid, allowing peptides bearing t-butyl-based side-chain protection to be cleaved intact. Conversion of the hydroxyl group into chloride [66] or trifluoroacetyl [67] provides linkers that have been used for immobilization of various nucleophiles, including alcohols, N-protected hydroxylamines, phenols, purines, amines, anilines and thiols [66-68], The stability of the cation derived from this tinker is such that even thiols and amines can be cleaved from this tinker with TFA (Figure 14.12). 

The following procedure is described for 4-formylphenoxy acetic acid, which is the precursor for the monoBAL handle, but it can equally be used for the o-BAL handle, see Chapter 9. However, treatment with cone. TFA will release the peptide from the support, thus providing the phosphopeptide directly in solution. Other linkers, such as Rink amide or Wang-type handles, can also be used for the Fmoc-SPPS of peptides in solution however, the first amino acid is then anchored by conventional N-acylation. 

---