Synthesis and Conformational Analysis of Methyl N‐Alanyl‐1′‐aminoferrocene‐1‐carboxylate

Abstract

Structurally different ferrocene peptides I-VI exhibit considerable conformational differences. This study has explored the structural properties of VII [Y-AA-Fca-OMe; Y = di-tert-butyl dicarbonate (Boc), acetyl (Ac); AA = L-Ala, D-Ala; Fca = 1Ј-aminoferrocene-1-carboxylic acid] with an exchanged sequence of constituent amino acids relative to VI (Y-Fca-AA-OMe; Y = Boc, Ac; AA = L-Ala, D-Ala). The ferrocene peptides VII were obtained by coupling C-protected Fca with Boc-L-Ala-OH and Boc-D-Ala-OH, respectively. The Boc protecting groups of the obtained conjugates Boc-AA-Fca-OMe (2a, AA = L-Ala; 2b, AA = D-Ala) were converted to sterically less demanding Ac groups to give Ac-AA-Fca-1820 Avance 300 MHz spectrometer in CDCl 3 solutions with Me 4 Si as the internal standard. Double resonance experiments (COSY, NOESY, and HMBC) were performed in order to assist in signal assignment. CD spectra were recorded using a Jasco-810 spectropolarimeter in CH 3 CN. Molar ellipticity coefficients, [θ], are in degrees, concentration, c, is given in molL -1 , and path length, l, is given in cm, to give units for [θ] of deg cm 2 dmol -1 . Computational Details:The starting geometries of 2a and 3a were generated by the MacroModel v9.8 [26] molecular modeling program using several different search methods and force fields. The conformers were fully optimized at the B3LYP/LanL2DZ level of theory. [23] The most stable were reoptimized in chloroform (using IEF-PCM to describe implicit solvent effects) with the B3LYP method and 6-311+G(d,p) basis set. [24] Iron was modeled using the ECP set LanL2DZ. Quantum mechanical calculations were performed with Gaussian 09, v.A.02. [27] Molecules were visualized using GaussView [28] and Chem 3D (CambridgeSoft, Cambridge, MA) programs. The topological analysis of the selected compounds was performed with the AIM2000 program. [29] Boc-AA-Fca-OMe (2a/2b): The syntheses of 2a and 2b were performed according to our recent paper: [9] the fully protected ferrocene amino acid Boc-Fca-OMe [5] (1) was N-deprotected by gaseous HCl in EtOAc to give the hydrochloride salt, which was treated with NEt 3 and coupled with Boc-AA-OH (AA = l-, d-Ala, previously activated by using EDC and HOBt). After standard workup and TLC-purification, Boc-l-Ala-Fca-OMe (2a) and Boc-d-Ala-Fca-OMe (2b) were obtained as orange resins.

The conjugates of ferrocene-1,1′-diamine and amino acids. A novel synthetic approach and conformational analysis

“…13 The N-terminus of alanine was protected by using sodium hydroxide, aqueous dioxane and di-tertbutyldicarbonate to give Boc-Ala-OH. The CH 2 Cl 2 used for synthesis and FTIR was dried (P 2 O 5 ), distilled over CaH 2 , and stored over molecular sieves (4 Å).…”

“…13 In order to prevent racemisation of its chiral center, the saponification of ester group of compound 4 was performed with an equimolar amount of base under restricted conditions (1h/ 80°C). 13 In order to prevent racemisation of its chiral center, the saponification of ester group of compound 4 was performed with an equimolar amount of base under restricted conditions (1h/ 80°C).…”

“…13,48,54 Herein, we have decided to use the same approach to [c] Cg1 is centroid of the C6-C10 ring. 13,48,54 Herein, we have decided to use the same approach to [c] Cg1 is centroid of the C6-C10 ring.…”

Synthesis and structure analysis of ferrocene‐containing pseudopeptides

“…The sign of the band at 460 nm indicates the preferential helicity adopted by the Fc moiety, which is normally controlled by one or more intramolecular hydrogen bonds (as it occurs in 1,1′‐disubstituted Fc) . In our case, the X‐ray structure of 1 (Figures and ) features an H···π interaction between one cyclopentadienyl (Cp) and the adjacent Phe ring which may be responsible for the chirality transfer to the Fc.…”

“…Additional characterization of 1 and 2 was carried out by electronic and vibrational circular dichroism (ECD and VCD) . ECD in particular has been thoroughly employed to study Fc‐peptide conjugates, including Fc–FF . VCD, apart from sensing peptide conformation, may benefit from the presence of the Fc moiety as mentioned in the introduction.…”