19 research outputs found
Ligations from Tyrosine Isopeptides via 12- to 19-Membered Cyclic Transition States
Efficient syntheses of <i>O</i>-acyl Tyr-peptides allow
chemical long-range ligation (<i>O</i>-acyl to <i>N</i>-acyl transfer) via each of 12- to 19-membered cyclic transition
states. The results represent the first examples of successful isopeptide
ligations starting from <i>O</i>-acyl Tyr-peptides
Governing Parameters of Long-Range Intramolecular <i>S</i>âtoâ<i>N</i> Acyl Transfers within (<i>S</i>)âAcyl Isopeptides
The governing parameters for the long-range intramolecular <i>S</i>-to-<i>N</i> acyl transfer in (<i>S</i>)-acyl isopeptides are shown by computational and statistical methods
(principal component analysis and cluster analysis) to be driven by
enthalpic and geometric effects over the range <i>n</i> =
5â20. The results emphasize the dependency of Î<i>G</i><sup>âĄ</sup> on the geometrical parameters governing
the approach of the reactive termini and the importance of stabilizing
intramolecular hydrogen bonds in the transition states (TSs), rather
than the effects of TS ring-size. The competition between the intra-
(uni-) and inter- (bi)Âmolecular acyl transfers were studied for representative
examples
Boiling Points of Ternary Azeotropic Mixtures Modeled with the Use of the Universal Solvation Equation and Neural Networks
Azeotropic mixtures, an important class of technological
fluids, constitute a challenge to theoretical modeling of their properties.
The number of possible intermolecular interactions in multicomponent
systems grows combinatorially as the number of components increases.
Ab initio methods are barely applicable, because rather large clusters
would need to be calculated, which is prohibitively time-consuming.
The quantitative structureâproperty relationships (QSPR) method,
which is efficient and extremely fast, could be a viable alternative
approach, but the QSPR methodology requires adequate modification
to provide a consistent treatment of multicomponent mixtures. We now
report QSPR models for the prediction of normal boiling points of
ternary azeotropic mixtures based on a training set of 78 published
data points. A limited set of meticulously designed descriptors, together
comprising the Universal Solvation Equation (<i>J. Chem. Inf.
Model.</i> <b>2009</b>, <i>49</i>, 634), was
used to provide input parameters for multiple regression and neural
network models. The multiple regression model thus obtained is good
for explanatory purposes, while the neural network model provides
a better quality of fit, which is as high as 0.995 in terms of squared
correlation coefficient. This model was also properly validated and
analyzed in terms of parameter contributions and their nonlinearity
characteristics
Cu(I)-Catalyzed Regioselective Synthesis of Pyrazolo[5,1-<i>c</i>]-1,2,4-triazoles
Cycloadditions of terminal alkynes to 1,2,4-triazolium <i>N</i>-imides in the presence of base and CuÂ(I) afford pyrazoloÂ[5,1-<i>c</i>]-1,2,4-triazoles regioselectively. The scope of alkynes,
the influence of the electronic nature of the leaving group, and variations
in the 1-alkyl substituent were examined. Quantum chemical calculations
were employed to explain the distinct reactivity of the propiolates
Synthesis of Taurine-Containing Peptides, Sulfonopeptides, and <i>N</i>- and <i>O</i>âConjugates
Taurine-containing water-soluble
peptidomimetics were designed
and synthesized. <i>N</i>-terminal taurine acylations allowed
synthesis of a number of taurine-containing peptides. <i>N</i>-protection of taurine with Cbz and SO<sub>2</sub>-activation with
benzotriazole followed by coupling with various amino esters, dipeptides
and nucleophiles provided taurine <i>N</i>- and <i>O</i>-conjugates and sulfonopeptides
Push-Pull Triazenes Derived from 1â(Benzylideneamino)- and 1â(Sulfonimido)-azolylidenes
In-situ-generated neutral 1-(benzylideneamino)-
and novel anionic
1-(sulfonimido)-azolylidenes react with organic azides to afford diverse
classes of push-pull triazenes and triazene salts. The scope of the
heterocyclic core and substituents at the N1 and N3 positions of NHC
precursors together with the thermal properties of resulting compounds
were examined
Benzotriazole-Mediated Synthesis of Aza-peptides: En Route to an Aza-Leuenkephalin Analogue
Novel <i>N</i>-(<i>N</i>-Pg-azadipeptidoyl)Âbenzotriazoles <b>20a</b>â<b>e</b> couple efficiently with α-amino
acids <b>21a</b>â<b>e</b>, dipeptides <b>22a</b>â<b>c</b>, aminoxyacetic acid <b>23a</b>, depsidipeptide <b>23b</b>, and α-hydroxy-ÎČ-phenylpropionic acid <b>27</b> yielding, respectively, azatripeptides <b>24a</b>â<b>g</b>, azatetrapeptides <b>25a</b>,<b>b</b>, a hybrid azatripeptide with an oxyamide bond <b>26a</b>,
a hybrid azatetrapeptide with an ester bond <b>26b</b>, and
a hybrid azatripeptide with an ester bond <b>28</b>. A new protocol
for the synthesis of <i>N</i>-Pg-azatripeptides <b>33a</b>,<b>b</b> and <b>35a</b>,<b>b</b>, each containing
a natural amino acid at the <i>N</i>-terminus, avoids the
low coupling rates of the aza-amino acid residue and enables the solution-phase
synthesis of an azaphenylalanine analogue of Leu-enkephalin <b>40</b>
Synthesis and Direct C2 Functionalization of Imidazolium and 1,2,4âTriazolium <i>N</i>âImides
Pd-catalyzed direct C2 arylation
and Cu-catalyzed direct one-pot
alkynylation/intramolecular cyclization of azolium <i>N</i>-imides are reported. Various acetylenes, aryl iodides, and 1-alkyl
substituents were examined. The mild protocol allows direct C2 arylation
of azolium <i>N</i>-imides without the use of specialized
reagents together with novel one-pot regioselective preparations of
imidazole-pyrazolo and pyrazolo-1,2,4-triazole ring systems. The electronic
properties of selected examples were examined by fluorescence spectroscopy
Oxyazapeptides: Synthesis, Structure Determination, and Conformational Analysis
Herein we report the synthesis, X-ray
structure determination,
and conformational analysis of a novel class of heteroatom-modified
peptidomimetics, which we shall call âoxyazapeptidesâ.
Substituting the typical native N-C<sup>α</sup> bond with an
O-N<sup>α</sup> bond creates a completely new, previously unknown
family of peptidomimetics, which are hydrolytically stable and display
very interesting conformational behavior. Force field calculations
revealed that the barrier to rotation around the O-N<sup>α</sup> bond in oxyazapeptides is five times lower than that around the
N-N<sup>α</sup> bond in azapeptides. Also, conformational analysis
supported by X-ray suggests that the oxyaza moiety can effectively
induce ÎČ-turns, which can make the newly discovered oxyazapeptide
scaffold a useful tool for drug discovery and for design of biologics
MFTA model: (a) molecular super-graph, (b) factor dynamics, and (c) fit plot.
<p>(a) The molecular supergraph is shown with two superimposed structures: DEET and <i>N</i>-cyclohexyl-<i>N</i>-ethyl-3-methylbutanamide (5m). The manner in which structures appear on MSG depends on how they can be superimposed onto the MSG as a whole. (b) The plot displays the change in correlation coefficient (R) and squared cross-validation coefficient (Q<sup>2</sup>) change as the number of factors changes. The best model is the one with the minimum possible number of factors and with R and Q<sup>2</sup> at their highest values.</p