Showing papers by "Carlos Cativiela published in 2000"
TL;DR: In this paper, the authors synthesize the model dipeptides tBuCO- l -Pro-c3diPhe-NHiPr, where c3DiPhe represents (2S, 3S)- and (2R, 3R)-1-amino-2,3-diphenylcyclopropanecarboxylic acid, two cyclopropane analogues of phenylalanine.
35 citations
TL;DR: This study reinforced previous conclusions that peptides based on alpha-amino acids with a Calpha-methyl substituent and aCalpha-linear alkyl substituents are characterized by a strong tendency to fold into turn and helical structures.
Abstract: Using different stereoselective chemical and chemoenzymatic approaches we synthesized the chiral, Calpha-methylated alpha-amino acid L-(alphaMe)Nva with a short, linear side-chain. A set of terminally protected model peptides to the pentamer level containing either (alphaMe)Nva or Nva in combination with Ala and/or Aib was prepared using solution methods and characterized fully. Two (alphaMe)Nva peptides were also synthesized using side-chain hydrogenation of the corresponding Calpha-methyl, Calpha-allylglycine (Mag) peptides. A detailed solution and crystal-state conformational analysis based on FT-IR absorption, 1H NMR and X-ray diffraction techniques allowed us to define that: (i) (alphaMe)Nva is an effective beta-turn and 3(10)-helix former; and (ii) the relationship between (alphaMe)Nva chirality and the screw sense of the turn/helix formed is that typical of protein amino acids, i.e. L-(alphaMe)Nva induces the preferential formation of right-handed folded structures. In more general terms, this study reinforced previous conclusions that peptides based on alpha-amino acids with a Calpha-methyl substituent and a Calpha-linear alkyl substituent are characterized by a strong tendency to fold into turn and helical structures.
29 citations
TL;DR: Findings indicate that, despite the common Cα-methylated and Cβ-branched features, ( αMe)Dip and (αMe)Val are characterized by partially divergent conformational bias.
Abstract: For the first time a number of terminally protected model peptides (to the pentamer level) of the sterically demanding α-amino acid Cα-methyl,Cα-diphenylmethylglycine, (αMe)Dip, in combination with either Ala or Gly residues, have been synthesized (by solution methods) and fully characterized. In a parallel synthesis the corresponding peptides based on the related α-amino acid Cα-methyl,Cα-isopropylglycine, (αMe)Val, have also been prepared. The results of a comparative conformational analysis, performed by using FTIR absorption, 1H NMR, and X-ray diffraction techniques, favour the conclusion that, in contrast to the potent β-turn and 310-helix promoter (αMe)Val, (αMe)Dip may induce either a folded or a fully extended conformation. These findings indicate that, despite the common Cα-methylated and Cβ-branched features, (αMe)Dip and (αMe)Val are characterized by partially divergent conformational bias.
12 citations
TL;DR: MS/MS of [MH](+) ions allows a clear characterization of the different stereoisomers, which give rise to specific fragmentation pathways, rationalized with respect to the structure of the neutral molecules.
Abstract: The mass spectrometric behaviour of (1S,2R)-, (1R,2R)-, (1R,2S)- and (1S,2S)-2-[(S)-2,2-dimethyl-1, 3-dioxolan-4-yl]-1-spiro-?4'[2'-phenyl-5'(4'H)-oxazolone]? cyclopropane (2) and (1S,2R)-, (1R,2R)-, (1R,2S)- and (1S, 2S)-methyl-1-benzamido-2-[(S)-2,2-dimethyl-1, 3-dioxolan-4-yl]cyclopropanecarboxylate (3) was studied under atmospheric pressure ionization conditions and by multi-stage mass spectrometric (MS(n)) experiments performed with an ion trap. Interestingly, by using methanol as solvent, compounds 2 lead to [M + H + CH(3)OH](+) ions which, as proved by collisional experiments, exhibit the same structure of the corresponding compound 3. MS/MS of [MH](+) ions allows a clear characterization of the different stereoisomers, which give rise to specific fragmentation pathways, rationalized with respect to the structure of the neutral molecules.
3 citations
TL;DR: In this article, the synthesis of enantiomerically pure (S )- and ( R )-α-vinylalanines and ( S )-and ( R ε)-α-ethynylalanine, four quaternary α-amino acids, using a straightforward synthetic route and starting from (S ǫ)- and (R )- N -Boc-N,O -isopropylidene-α -methyl serinals.
Abstract: This report describes the synthesis of enantiomerically pure ( S )- and ( R )-α-vinylalanines and ( S )- and ( R )-α-ethynylalanines, four quaternary α-amino acids, using a straightforward synthetic route and starting from ( S )- and ( R )- N -Boc- N,O -isopropylidene-α-methylserinals.
1 citations
TL;DR: The structures of two conformationally restricted 4,5-dihydroxynorvaline analogues with a norbornane skeleton, namely methyl (1S,2S,3R,4R)-2-benzamido-3-(1,2-di-Hydroxyethyl)bicyclo[2.2.1]heptane-2-carboxylate, C18H23NO5, and methyl
Abstract: The structures of two conformationally restricted 4,5-dihydroxynorvaline analogues with a norbornane skeleton, namely methyl (1S,2S,3R,4R)-2-benzamido-3-(1,2-dihydroxyethyl)bicyclo[2.2.1]heptane-2-carboxylate, C18H23NO5, and methyl (1R,2S,3R,4S)-2-benzamido-3-(1,2-dihydroxyethyl)bicyclo[2.2.1]heptane-2-carboxylate, C18H23NO5, exhibit a conformation in the helical region of the φ,ψ map but their handedness is opposite. In both cases, the torsion angles (χ1,1) giving the relative orientation of the 1,2-dihydroxyethyl group of the amino acid side chain and the benzamide group of the peptide chain indicate that these groups adopt a nearly eclipsed conformation. Both compounds show a complex hydrogen-bonding pattern.
1 citations
TL;DR: In this article, a new family of constrained 1-amino-4-hydroxycyclohexane-1-carboxylic acid (1 and 2) was achieved through selective transformations of the functional groups of the corresponding enone cycloadduct provided by the Diels-Alder cycloaddition of Danishefsky's diene to methyl 2-acetamidoacrylate.
Abstract: The synthesis of both stereoisomers of 1-amino-4-hydroxycyclohexane-1-carboxylic acid (1 and 2), a new family of constrained hydroxy-α,α-disubstituted-α-amino acids, is achieved through selective transformations of the functional groups of the corresponding enone cycloadduct provided by the Diels–Alder cycloaddition of Danishefsky’s diene to methyl 2-acetamidoacrylate. The stereochemistry of intermediates 8 and 9 in the synthesis of hydroxy-α-amino acids 1 and 2 was unambiguously confirmed by X-ray structure determination.
1 citations
TL;DR: In this paper, N -Benzylimines derived from conveniently protected (R )-glyceraldehyde underwent diastereoselective phenylmagnesium bromide addition to afford the corresponding aminodiols, whose absolute configuration at the newly formed stereogenic carbon depends on the O -protecting group.
Abstract: N -Benzylimines derived from conveniently protected ( R )-glyceraldehyde underwent diastereoselective phenylmagnesium bromide addition to afford the corresponding aminodiols, whose absolute configuration at the newly formed stereogenic carbon depends on the O -protecting group. These compounds can be easily transformed into optically pure N - tert -butoxycarbonyl-1-phenyl-2,3-epoxy-1-propylamines, which are key intermediates in the synthesis of 2- tert -butoxycarbonylamino-3-acetyloxypentanoates of erythro and threo configuration.
TL;DR: The structures of two conformationally restricted 4,5-di-hydroxy-norvaline analogues with a norbornane skeleton, namely methyl (1S,2S,3R,4R)-2-benz-amido-3-(1,2-dihydroxyethyl)-bi-cyclo[2.2.1] and C18H23NO5, exhibit a conformation in the helical region of the φ,ψ map but their handedness is opposite as mentioned in this paper.
Abstract: The structures of two conformationally restricted 4,5-dihydroxynorvaline analogues with a norbornane skeleton, namely methyl (1S,2S,3R,4R)-2-benzamido-3-(1,2-dihydroxyethyl)bicyclo[2.2.1]heptane-2-carboxylate, C18H23NO5, and methyl (1R,2S,3R,4S)-2-benzamido-3-(1,2-dihydroxyethyl)bicyclo[2.2.1]heptane-2-carboxylate, C18H23NO5, exhibit a conformation in the helical region of the φ,ψ map but their handedness is opposite. In both cases, the torsion angles (χ1,1) giving the relative orientation of the 1,2-dihydroxyethyl group of the amino acid side chain and the benzamide group of the peptide chain indicate that these groups adopt a nearly eclipsed conformation. Both compounds show a complex hydrogen-bonding pattern.