engleski

Synthesis of amino acids and oligopeptides containing skeletal 1, 1'-ferrocenylene unit

As a part of our studies on ferrocene containing amines, oligoamides and amino acids we have recently published efficient synthesis of 1'-aminoferrocene-1-carboxylic acid (2a) and its derivatives 3a-5a [1]. The first part of this report is dealing with syntheses of 2b and 2c &#8211 ; the higher homologues of amino acid 2a. Crucial intermediates ester-amides 1b/1c were prepared by succinylation of methyl ferrocenecarboxylate, reduction of keto acid formed, and reactions of the ester-acids obtained with aqueous Et_3N/ClCOOEt/NaN_3. Curtius rearrangement of 1b/1c in Ac_2O, with subsequent hydrolysis, gave 3b/3c. Further, 1b/1c were converted by heating in t-BuOH, and hydrolysis of ester function, into 5b/5c, which were cleaved by TFA into the corresponding salts. In the second part of investigation N-Boc derivatives 5a-c were coupled with several natural amino acids (Gly, Ala, Leu...) using DCC/HOBt method to give dipeptides 6a-c. HCl/MeOH converted these compounds into hydrochlorides, which reacted with N-Boc protected natural amino acids in presence of DCC/HOBt/Et_3N giving the corresponding tripeptides 7. In a similar way 5a-c and appropriately protected dipeptides (Gly-Gly, Gly-Ala...) gave oligopeptides 8 and 9. Structural studies of peptides prepared will be undertaken. Having in mind hydrogen-bonding ability of peptide strands one could expect difference in organization of rigid peptides of type a and b/c with flexible trimethylene spacer between ferrocene scaffold and NH or CO.

Ferrocene; Amino acid; Oligopeptide

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