Phenylacetamidomethyl resins

Mitchell AR, Kent SBH, Engelhard M, Merrifield R. A new synthetic route to tert-butyloxycarbonylaminoacyl-4-oxymethyl)phenylacetamidomethyl-resin, an improved support for solid-phase peptide synthesis. J Org Chem... 

PHENYLACETAMIDOMETHYL RESIN FOR SYNTHESIS OF PEPTIDES USING BOC/BZL CHEMISTRY... 

FIGURE 5.15 Synthesis of PAM (phenylacetamidomethyl) resin. (Merrifield et al., 1976). Use of PAM resin implies a Boc-amino acid anchored to oxymethylphenylacetamidomethyl-polystyrene through an ester linkage. The acetamido group renders the ester more stable to acid. 

For the hydrolysis of peptides linked to resins, the release of the C-terminal amino acid is strongly dependent upon the type of resin and amino acid residue. For this purpose the use of propanoic acid/12M HC1 (1 1 )[6 is recommended. More studies, however, indicate hydrolysis with TFA/12M HC1 (1 3) at 160°C is more appropriate since quantitative release of the most stable Phe residue from benzhydrylamine- (BHA-), 4-methylbenzhydrylamine-(pMeBHA-), and 4-(hydroxymethyl)phenylacetamidomethyl-resins occurs in 20, 6, and 5 h, respectively, compared to the 30,18, and 18h required with propanoic acid/12M HC1 (1 1)) ... 

In the studies described below cyclic head-to-tail peptides were synthesized by standard solid-phase synthesis utilizing Boc chemistry 27 All syntheses were carried out with Boc-Pro-phenylacetamidomethyl resin. The use of Pro as the C-terminus residue was required so as to prevent racemization during the cyclization reaction (see Section 13.3.1.1). 

Hydroxymethylphenylacetic acid [130] PAM resin Phenylacetamidomethyl resin Cleavage - THF/HjO, LiBr/DBU - MeOH/DBU/ LiBr, EtOH/Ti(OEt), Product after cleavage - Carboxylic acid - Carboxylic acid ester... 

Resins Boc-glycine-phenylacetamidomethyl (Boc-Gly-PAM) resin and Fmoc-Rink amide MB HA resin. It is preferable to use 100-200 mesh size resin as it drains more easily in the reaction vessel. To calculate the amount of resin for the synthesis, Eq. 1 is used ... 

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