Conformational Analysis of β‐Lactam‐Containing Ferrocene Peptides

Abstract

AbstractThe homochiral 3‐amino‐1‐(4‐methoxyphenyl)‐4‐phenyl‐β‐lactam (≡ Alm) was conjugated with Boc‐Ala to give Ala‐Alm (9) after Boc deprotection (Boc = tert‐butoxycarbonyl, Ala = alanine). Coupling of Fc‐COOH (1) and Boc‐Fca (10) with “dipeptide” 9 resulted in the formation of Fc‐CO‐Ala‐Alm (12) and the trisamide Boc‐Fca‐Ala‐Alm (13), respectively (Fc = ferrocenyl, Fca = 1′‐aminoferrocene‐1‐carboxylic acid). The reactions were accomplished by the HOBt/EDC procedure, and the products were obtained in good yields [HOBt = 1‐hydroxybenzotriazole, EDC = N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride]. Symmetrically 1,1′‐disubstituted “tetrapeptide” Fn(CO‐Ala‐Alm)2 (14) was prepared by reaction of ferrocene chloride 11 with 9 (Fn = 1,1′‐ferrocenediyl). Spectroscopic and theoretical analyses revealed that compounds 12, 13, and 14 are stabilized in solution by medium‐strong intramolecular hydrogen bonds. In all dominant conformations (DFT calculations) intrachain bonds spanning COFc and NHAlm are present (γ‐turns). Additional interchain hydrogen bonds NHAla···COBoc (13) and NHAla···COAla/NHAla···COAlm (14) give rise to ordered helical conformations of the ferrocene moieties.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)