Synthesis and Structure of Chiral Methoxypyrrole Amino Acids (MOPAS)

Abstract

A methoxypyrrole amino acid (MOPAS) resembling the structure of H₂N-Val-Δ-Ala-OEt in β-sheet conformation has been prepared by a chiral auxiliary approach. The X-ray structure analysis confirms the absolute configuration of the dipeptide mimic. Standard peptide coupling procedures allow coupling of the chiral MOPAS with natural amino acids or their extension by additional MOPAS units. A tight self-association of bis-MOPAS 13 in CDCl₃ and the affinity to Ac-Ala-Ile-OMe dipeptides illustrates the ability of the constrained dipeptide mimic MOPAS to interact with peptides.

Key words

heterocycles - amino acids - peptides - chiral auxiliaries - imines

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11

A derivative of 1 bearing a methyl group in position 2 may cyclize more easily. However, our attempts to transform this compound into the Schiff base corresponding to compound 2 were not successful.

15

The self-association of 10 is one order of magnitude higher if compared to a Boc-(MOPAS)₂-OEt missing the isopropyl substituent; see ref. 7a for data.

17

The self-association of 10 and the dipeptides were included in the binding model.