Trifluoroacetic acid → 3-Hydroxydecanoic acid
Reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C@@H:8]([OH:13])[CH2:9][C:10]([OH:12])=[O:11].C(O)(C(F)(F)F)=O.C=C[C@@H]1[C@@H]2C[C@@H]([C@H](O)C3C4C(=CC=CC=4)N=CC=3)N(CC2)C1>CN(C=O)C>[OH:13][CH:8]([CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])[CH2:9][C:10]([OH:12])=[O:11]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
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.
Sources & evidence
- ORD record
- ord-fa72c2d3ec524242bfbb9cc8bb75334b
- Source dataset
- uspto-grants-1992_12
- Patent number
- US05169862
Reaction notes
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