Question

What are the advantages and limitations of:

1. Merrifield resin (simple cross linked polystyrene-based resin)

2. PAM resin (4-hydroxymethyl-phenylacetamidomethyl resin)

3. BHA resin (benzhydrylamine resin)

Answer 1

Merrifield Resin

Advantages:

Polystyrene resins swell in solvents of low to medium polarity (DMF, DCM, toluene)

Don’t swell in polar, protic solvents (alcohol and water).

Disadvantages:

• Only temperatures under 130°C.
• No usage of very electrophilic reagents.
• The benzyl ester linkage between C terminal amino acid can be partially cleaved in deprotection step and important loss can occur in construction of long peptide chain.

PAM RESINS

ADVANTAGES:

To circumvent above loss in long peptide chain a Phenylacetamidomethyl linker is introduced between support and C terminal amino acid .

This linker provide stabilization at each step of deprotection and hence preventing loss during cinsconstruc of long peptide chain.

Limitations.

While preparing PAM RESIN there is esterification reaction between Boc amino acid and 4- hydroxymethyl phenylacetamidomethyl polystyrene resin in presence of DCC implies a Risk Of Racemization .

BHA resins .

Advantages

BHA/ MBHA (Benzhydrylamine / 4-Methylbenzhydrylamine)- Used for the synthesis of peptide amides by Boc SPPS

• Attachment of the first amino acid with standard methods of amide bond formation
• More stable.
• Cleavage of the carboxamides with HF or TFMSA.

BHA is more acid sensitive and the peptide amide can be released with HF or TFMSA under less drastic conditions.