engleski

Synthesis of Heteroannularly Substituted Ferrocene Amino Acid Containing Chiral Center

In continuation of our studies on ferrocene containing amines, oligoamides and amino acids we have recently described efficient syntheses of C- and N-protected amino acids 1 (m, n = 0, 3 ; p, r = 0 ; X = Ac, Cbz, Boc ; R = H, Me) [1, 2] and the derived conjugates with L-alanine 1 (p, r = 1-2) [3]. Prompted by these results we decided to prepare the similar amino acids of type 3 containing the chiral centre incorporated in the aminoaliphatic part of the molecule. In this context it seemed interesting to explore the diastereomeric induction in coupling reaction of the optically pure title amino acid with racemic alanine, as well as in combination of racemic 3 and L- and D-alanine using EDC/HOBt protocol or CLEC-subtilisin catalysis. Here we are reporting about preparation of 3 (n = 1) in multistep synthesis starting from methyl ferrocenecarboxylate. Acetylation of this ester and subsequent reduction gave methyl 1'-(1-hydroxyethyl)ferrocene-1-carboxylate. This compound underwent the malonic ester condensation, hydrolysis and decarboxylation into 1'-metoxycarbonyl-?-methyl-1-ferrocenepropionic acid ; the derived ester-azide 2 (n = 1) rearranged by refluxing in t-BuOH giving ester 3 (n = 1 ; X = Boc ; R = Me) which hydrolysed into corresponding acid (R = H). Yields of the described reactions were 55-88%.

ferrocene amino acid with chiral center; synthesis

nije evidentirano