Solid Phase Esterification

This method describes the esterification of peptides in sequence with the coupling of the terminal residue, a hydroxy acid, onto the next.

Step 1: Coupling of Hydroxy Acid onto Peptide

hydroxy%20couple.PNG

It's been found that standard coupling conditions/equivalencies are sufficient when coupling on a hydroxy acid.

  1. Rinse resin with DMF (3x), followed by swelling with DCM (3x)
  2. Dissolve hydroxy acid in DMF.
  3. Add DIPEA, followed by HOAt and HATU.
  4. Agitate for 45 min - 1 hr. and check on HPLC for completion

NOTE: Ionization of hydroxy acids might appear weaker in the MS.

Step 2: Esterification

esterification.PNG

NOTE: The esterification step requires dry technique.

  1. Swell resin with DCM and pull through with Argon.
  2. Add dry THF to resin and pull through with Argon.
  3. In separate vial, dissolve the next residue in dry THF. Then add in DMAP, followed by DIC.
  4. Allow the solution to react for 2-5 minutes.
  5. Add solution to resin, cap, and agitate for 1 hour.
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