| 1. |
- Hubatsch, Ina, et al.
(författare)
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Beta- and gamma-di- and tripeptides as potential substrates for the oligopeptide transporter hPepT1
- 2007
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:21, s. 5238-5242
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Tidskriftsartikel (refereegranskat)abstract
- The hPepT1-mediated transport properties of a series of 11 synthesized beta- and gamma-peptides have been studied in Caco-2 cells. The results show that several of the compounds interact with the peptide transporter, but only two beta-dipeptides act as substrates and are transported across the cell monolayers. These two are less-efficient substrates than alfa-peptides. Larger derivatives than beta-dipeptides do not act as hPepT1 substrates, but instead, they appear to be substrates for P-glycoprotein efflux.
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| 2. |
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| 3. |
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| 4. |
- Govender, Thavendran, et al.
(författare)
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Organocatalytic synthesis of chiral benzopyrans
- 2006
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Ingår i: Tetrahedron: Asymmetry. - : Elsevier BV. - 0957-4166. ; :17, s. 1763-1767
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Tidskriftsartikel (refereegranskat)abstract
- Benzopyrans, or chromenes, are widespread in nature and are considered to be a privileged scaffold in medicinal chemistry. Herein, we report the first organocatalyzed asymmetric synthesis of chiral benzopyrans. The benzopyran unit is constructed through a domino reaction involving an oxa-Michael attack of salicylic aldehyde derivatives onto a,B-unsaturated aldehydes, activated through iminium-ion formation with the organocatalyst, followed by an intramolecular aldol reaction and subsequent elimination of water. This overall reaction sequence provides benzopyrans with aromatic C-2 substituents in up to 60% enantioselectivity, while C-2 aliphatic analogues can be obtained in 90% enantiomeric excess, but with only 20% yield. The role of additives, as well as the possible racemization of the benzopyran, was also investigated.
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| 5. |
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| 6. |
- Hartikka, Antti, et al.
(författare)
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Synthesis and application of novel imidazole and 1H-tetrazolic acid containing catalysts in enantioselective organocatalyzed Diels-Alder reactions
- 2009
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Ingår i: Tetrahedron. - : Elsevier BV. - 0957-4166 .- 1362-511X. ; 20:16, s. 1871-1876
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Tidskriftsartikel (refereegranskat)abstract
- Herein we report studies on the organocatalytic Diels-Alder reaction using a variety of catalysts capable of activating alpha,beta-unsaturated carbonyl compounds for reactions with dienes. The structurally attractive catalysts 4 and 14 were utilized in the enantioselective organocatalytic Diels-Alder reactions. Catalyst 4 provided the products in fair yields and more importantly in good enantioselectivities of up to 83% ee. Catalyst 14 was synthesized in high yield and was assessed in the enantioselective organocatalytic Diels-Alder reaction. Catalyst 14 proved to be a highly active and selective catalyst providing the products in high yield and high enantioselectivities up to 95% ee. (C) 2009 Elsevier Ltd. All rights reserved.
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| 7. |
- Hartikka, Antti, et al.
(författare)
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Tetrazolic Acid Functionalized Dihydroindol : Rational Design of a Highly Selective Cyclopropanation Organocatalyst
- 2007
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 72:15, s. 5874-5877
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Tidskriftsartikel (refereegranskat)abstract
- Herein we wish to report our development of an improved catalyst (S)-(-)-indoline-2-yl-1H-tetrazole (1) for the enantioselective organocatalyzed cyclopropanation of α,β-unsaturated aldehydes with sulfur ylides. The new organocatalyst readily facilitates the enantioselective organocatalytic cyclopropanation, providing cyclized product in excellent diastereoselectivities ranging from 96% to 98% along with enantioselectivities exceeding 99% enantiomeric excess for all reacted α,β-unsaturated aldehydes. The new catalyst provides the best results so far reported for intermolecular enantioselective organocatalyzed cyclopropanation.
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| 8. |
- Hojabri, Leila, et al.
(författare)
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A new Imidazole-Containing Imidazolidinone Catalyst for Organocatalyzed Asymmetric Conjugate Addition of Nitroalkanes to Aldehydes
- 2007
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Ingår i: Advanced Synthesis and Catalysis. - : Wiley. - 1615-4150 .- 1615-4169. ; 349:4-5, s. 740-748
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Tidskriftsartikel (refereegranskat)abstract
- Herein we report a new organocatalyst for the asymmetric Michael addition of nitroalkanes to α,β-unsaturated aldehydes. This catalyst incorporates a basic imidazole group in addition to the secondary amine responsible for activation of the α,β-unsaturated carbonyl compounds via iminium ion formation. The new organocatalyst is capable of catalyzing the enantioselective carbon-carbon bond formation with a high degree of enantiocontrol providing products in enantiomeric excesses of up to 92% and yields of up to to 91 %. These results constitute the best results so far reported for organocatalyzed Michael additions of nitroalkanes to α,β-unsaturated aldehydes, and provide proof of principle that organocatalysts incorporating two internal basic moieties may find broad application in organocatalyzed Michael additions.
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| 9. |
- Norgren, Anna S., et al.
(författare)
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Biomolecular Recognition of Glycosylated β3-Peptides by GalNAc Specific Lectins
- 2007
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Ingår i: Journal of Molecular Recognition. - : Wiley. - 0952-3499 .- 1099-1352. ; 20:2, s. 132-138
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Tidskriftsartikel (refereegranskat)abstract
- The molecular recognition of a novel kind of hybrid conjugates, composed of artificial biomimetic β-peptide oligomers with an O-linked natural N-acetyl-galactosamine (the Tn-antigen) residue, by four different GalNAc specific lectins was investigated using surface plasmon biosensor technology. The influence of the peptide and the glycosyl moiety on the recognition was studied using two glycosylated β3-heptapeptides, a glycosylated α-heptapeptide, two β-amino acid containing dipeptides, and monomeric αGalNAc-O-Thr. Although all four lectins displayed a decreased affinity for the carbohydrate residue when attached to a peptide, as compared to the monomeric Tn-antigen, the peptide part was found to have distinct effects on the binding kinetics - indicating that varying degrees of protein-peptide interactions occurred in the recognition process. Likewise, the lectins did not discriminate between β3-peptides and the α-peptide, but the β- linkage of the galactose had a detrimental effect for at least two of the lectins.
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| 10. |
- Norgren, Anna S., 1978-
(författare)
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Conformational Stability!? : Synthesis and Conformational Studies of Unnatural Backbone Modified Peptides
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The beauty of the wide functionality of proteins and peptides in Nature is determined by their ability to adopt three-dimensional structures. This thesis describes artificial molecules developed to mimic secondary structures similar to those found crucial for biological activities.In the first part of this thesis, we focused on post-translational modifications of a class of unnatural oligomers known as β-peptides. Through the design and synthesis of a glycosylated β3-peptide, the first such hybrid conjugate was reported. In this first report, a rather unstable 314-helical structure was found. Subsequently, a collection of six new glycosylated β3-peptides was synthesized with the aim to optimize the helical stability in water.The ability of natural proteins, i.e. lectins, to recognize the carbohydrate residue on these unnatural peptide backbones was investigated through a biomolecular recognition study.The second part of this thesis concerns the design of conformationally homogeneous scaffolds, which could be of importance for biomedical applications. In paper V, four- and five-membered cyclic all-β3-peptides were investigated for this purpose. In a subsequent paper, a completely different strategy was employed; herein, the ability of a single β2-amino acid to restrict the conformational freedom of a cyclic α-peptide was studied. In the third part of this thesis, we synthesized and investigated the folding propensities of novel backbone modified oligomers, i.e. β-peptoids (N-substituted β-Ala) with α-chiral side chains.The collective results of these studies have established the procedures required for synthesis of glycosylated β-peptides and deepened our understanding of the factors governing folding among such oligomers. Moreover, it was established that β-amino acids can be a useful tool to increase conformational stability of cyclic peptides.
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