| 1. |
- Maricic, Suzana
(författare)
-
Metallocene based peptidomimetics and chiral catalysts
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several optically active organometallic Phe-AAn-Phe peptidomimetics and macrocyclic Phe-(Phe)n peptides have been synthesized by either intra- or intermolecular peptide bond formation of the corresponding bis(amino acid) derivatives. The key bis(amino acid) derivatives were available from an improved multi-step synthetic route, utilising Horner-Wadswort-Emmons olefination of organometallic aldehydes with phosphonylglycine reagents, enantioselective hydrogenation of didehydro amino acids and classical solution and/or solid phase peptide synthesis methodology. The stereochemically well characterised Phe-AAn-Phe peptidomimetics were incorporated in small neurotransmitter peptides, substance P and Leu(5)-enkephalin, with the goal to test whether the effect of the incorporation mimic the bioactive conformations. Conformational analysis of the peptide analogues was undertaken with computational energy minimisation, CD and various NMR-experiments. It revealed that the modification of substance P and Leu(5)-enkephalin induced random coil and b-turn like conformations, respectively. NMR titration and UV-Vis spectroscopic studies of ferrocene or ruthenocene based derivatives of phenylalanine, indicated that in contrast to ruthenocenylamino acids the ferrocenylamino acids were easily air oxidised in aqueous solution at pH?{5-7}. A series of chiral ferrocene based mono- and bis(amino alcohol) derivatives were also synthesized from the mono- and bis(amino acids), respectively. These were further evaluated as catalysts in asymmetric addition of diethylzinc to benzaldehyde. The results revealed that indeed all ferrocene based amino alcohol derivatives worked as catalysts and that the catalytic effect was not positively influenced by the introduction of one extra amino alcohol arm.
|
|
| 2. |
- Maricic, Suzana, et al.
(författare)
-
Synthesis and conformational analysis of optically active ferrocene containing macrocyclic peptides
- 2002
-
Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 1520-6904 .- 0022-3263. ; 67:22, s. 7600-7606
-
Tidskriftsartikel (refereegranskat)abstract
- Two macrocyclic peptides 3 and 4 were formed during lactamization of 1,1'-ferrocenylbis(alanine) 1. Isolation, structure determination, and conformational analysis of 3 and 4 are reported as well as a controlled stepwise synthesis of 4 also including an improved route to 1. On the basis of their H-1 NMR spectra recorded at 300 K in DMSO-d(6), the dimer 3 and trimer 4 were found to be C-2 and C-3 symmetric, respectively. As appeared from computational analysis, the low-energy conformations of the macrocyclic peptides were nonsymmetric. Cyclic voltammetry revealed that the ferrocenyl moieties in 3 or 4 are electrochemically equal to ferrocene.
|
|
| 3. |
- Maricic, Suzana, et al.
(författare)
-
Synthesis and conformational studies of a Leu-enkephalin amide analogue containing a ferrocene substructure
- 2002
-
Ingår i: Tetrahedron. - 0040-4020. ; 58:15, s. 3085-3093
-
Tidskriftsartikel (refereegranskat)abstract
- Solution phase synthesis of a constrained Leu(5)-enkephalin amide analogue 10 is reported, in which the cyclic ferrocenyl containing subunit 7 was introduced as a mimetic of the tetrapeptide Tyr-Gly-Gly-Phe unit. Temperature dependence of the chemical shift of the amide protons of 10 indicated a hydrogen bond between the same amino acid residues as observed for the natural Leu-enkepalin in the single-bend conformation. The rotational barrier (DeltaG(c)(not equal)=16.8 kcal/mol) of the C-terminal amide group, which was determined by DNMR spectroscopy, and NOESY experiments indicated that the two termini were more distant as compared to the single-bend conformation of natural Leu-enkephalin amide. (C) 2002 Elsevier Science Ltd. All rights reserved.
|
|
