Synthesis and Amino Acid Chain Extension of 1-Acylated Hydroxymethylpyrroles

Abstract

Acylation of pyrrole-2-carbaldehyde (3) with an N-phthaloyl amino acid chloride, N,N-diisopropylethylamine and 4-dimethylaminopyridine (dmap) gave the 1-acylpyrrole-2-carbalde-hydes (4a-c). The 1-acylated pyrroles (4d-i), (8) and (9) were similarly prepared in good yields from the relevant pyrrole derivative using dmap and either an acid chloride/N,N- diisopropylethylamine or an anhydride/triethylamine. Reduction of (4a-f) with zinc borohydride gave the 1-acylated hydroxymethylpyrroles (5a-f). A coupling of (5a) with N-Cbz-L-Val-L-Val-OH under Mitsunobu conditions gave the tetrapeptide analogue (11).