Hydrochloric Acid → 4-(4-Hydroxybenzoyl)-L-phenylalanine

Participants

Reaction Steps

FIG. 1 is a schematic showing the synthesis of HBPA. 4-(Chloromethyl)benzoyl chloride (II) is made by refluxing 4-(chloromethyl)benzoic acid with oxalyl chloride in benzene. Mixing this compound with pyridine with gentle heating using a steam bath followed by ice quench gave 4-chloro-methylbenzoic anhydride (III). 4-Chloromethylbenzoic anhydride (III) is reacted with phenol in polyphosphoric acid to give the 4-chloromethylbenzoyl ester of 4-chloromethyl-4'-hydroxybenzophenone (IV). Reacting IV with ethylacetamidocyanoacetate and subsequent hydrolysis with concentrated HCl gives racemic p-(4-hydroxybenzoyl)phenylalanine (HBPA, VI). D,L-HBPA is derivatized using standard Fmoc chemistry for incorporation into the peptide (e.g., at position 8 of substance P) by solid-phase synthesis. Radioiodination of L-HBPA8 -SP is accomplished using Chloramine-T. See "Experimental Procedures" for details. HBPA can also be prepared by procedures disclosed in Horner and Medem., Chem. Ber., 85:520 (1952), the teachings of which are incorporated herein by reference.

Provenance & Evidence