Trifluoroacetic acid → 3-Hydroxydecanoic acid

Participants

Reaction Steps

Linear peptide (18) was completed by acylating the peptide resin with the Pfp-ester of D-3-hydroxydecanoic acid in DMF. Again, the use of Pfp ester activation allowed the acid to be coupled with its hydroxyl unprotected. 3-Hydroxydecanoic acid (mp 55°-56° C., 57° C.)21 was synthesized from n-octyl aldehyde by reaction with lithium tert-butyl acetate22 followed by TFA hydrolysis and resolution as the (-)-cinchonidine salt (mp 119°-120° C., 119°-120° C.) which upon neutralization gave (-)-D-3-hydroxydecanoic acid ([a]D =-21.4° C. (c 1.0, CHCl3); lit. [a]D=-17.5°).19The final peptide was cleaved from the resin with TFA (50% in CH2Cl2, 30 min) and lyophilized from dioxane to yield the crude peptide (18). This was readily purified by reverse phase HPLC using a C18 column and an H2O-acetonitrile gradient system containing 0.1% TFA, with the resulting peptide being relyophilized from dilute anhydrous dioxane --HCl to yield (18).HCl as a white solid in 25% overall yield based on resin substitution.

Provenance & Evidence