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>‑to‑<i>N</i> Acyl Transfers within (<i>S</i>)‑Acyl 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> = 5–20. The results emphasize the dependency of Δ<i>G</i>^‡ 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)­molecular 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 structure–property 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 Cu­(I) afford pyrazolo­[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>‑Conjugates

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 SO₂-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 1‑(Benzylideneamino)- and 1‑(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)­benzotriazoles <b>20a</b>–<b>e</b> couple efficiently with α-amino acids <b>21a</b>–<b>e</b>, dipeptides <b>22a</b>–<b>c</b>, aminoxyacetic acid <b>23a</b>, depsidipeptide <b>23b</b>, and α-hydroxy-β-phenylpropionic acid <b>27</b> yielding, respectively, azatripeptides <b>24a</b>–<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 1,2,4‑Triazolium <i>N</i>‑Imides

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 “oxyazapeptides”. Substituting the typical native N-C^α bond with an O-N^α 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^α bond in oxyazapeptides is five times lower than that around the N-N^α bond in azapeptides. Also, conformational analysis supported by X-ray suggests that the oxyaza moiety can effectively induce β-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 (Q²) change as the number of factors changes. The best model is the one with the minimum possible number of factors and with R and Q² at their highest values.</p