Analysis of ergonomics problems contact-centers

The analysis of the ergonomic problems of the contact center. It allocates main factors of influence on man- operator

Oligomers of a 5-Carboxy-methanopyrrolidine β-Amino Acid. A Search for Order

CD spectra for homooligomers (n = 4, 6, 8) of (1S,4R,5R)-5-syn-carboxy-2-azabicyclo[2.1.1]hexane (MPCA), a methano-bridged pyrrolidine β-carboxylic acid, suggest an ordered secondary structure. Even in the absence of internal hydrogen bonding, solution NMR, X-ray, and in silico analyses of the tetramer are indicative of conformations with trans-amides and C5-amide-carbonyls oriented toward the C4 bridgehead. This highly constrained β-amino acid could prove useful in the ongoing development of well-defined foldamers

Oligomers of a 5-Carboxy-methanopyrrolidine β-Amino Acid. A Search for Order

CD spectra for homooligomers (n = 4, 6, 8) of (1S,4R,5R)-5-syn-carboxy-2-azabicyclo[2.1.1]hexane (MPCA), a methano-bridged pyrrolidine β-carboxylic acid, suggest an ordered secondary structure. Even in the absence of internal hydrogen bonding, solution NMR, X-ray, and in silico analyses of the tetramer are indicative of conformations with trans-amides and C5-amide-carbonyls oriented toward the C4 bridgehead. This highly constrained β-amino acid could prove useful in the ongoing development of well-defined foldamers

Oligomers of a 5-Carboxy-methanopyrrolidine β-Amino Acid. A Search for Order

CD spectra for homooligomers (n = 4, 6, 8) of (1S,4R,5R)-5-syn-carboxy-2-azabicyclo[2.1.1]hexane (MPCA), a methano-bridged pyrrolidine β-carboxylic acid, suggest an ordered secondary structure. Even in the absence of internal hydrogen bonding, solution NMR, X-ray, and in silico analyses of the tetramer are indicative of conformations with trans-amides and C5-amide-carbonyls oriented toward the C4 bridgehead. This highly constrained β-amino acid could prove useful in the ongoing development of well-defined foldamers

Oligomers of a 5-Carboxy-methanopyrrolidine β-Amino Acid. A Search for Order

CD spectra for homooligomers (n = 4, 6, 8) of (1S,4R,5R)-5-syn-carboxy-2-azabicyclo[2.1.1]hexane (MPCA), a methano-bridged pyrrolidine β-carboxylic acid, suggest an ordered secondary structure. Even in the absence of internal hydrogen bonding, solution NMR, X-ray, and in silico analyses of the tetramer are indicative of conformations with trans-amides and C5-amide-carbonyls oriented toward the C4 bridgehead. This highly constrained β-amino acid could prove useful in the ongoing development of well-defined foldamers

Synthesis of 5-Fluoro- and 5-Hydroxymethanoprolines via Lithiation of <i>N</i>-BOC-methanopyrrolidines. Constrained C^γ-Exo and C^γ-Endo Flp and Hyp Conformer Mimics

Proline derivatives with a C^γ-exo pucker typically display a high amide bond trans/cis (<i>K</i>_T/C) ratio. This pucker enhances n→π* overlap of the amide oxygen and ester carbonyl carbon, which favors a trans amide bond. If there were no difference in n→π* interaction between the ring puckers, then the correlation between ring pucker and <i>K</i>_T/C might be broken. To explore this possibility, proline conformations were constrained using a methylene bridge. We synthesized discrete gauche and anti 5-fluoro- and 5-hydroxy-<i>N</i>-acetylmethanoproline methyl esters from 3-syn and 3-anti fluoro- and hydroxymethanopyrrolidines using directed α-metalation to introduce the α-ester group. NBO calculations reveal minimal n→π* orbital interactions, so contributions from other forces might be of greater importance in determining <i>K</i>_T/C for the methanoprolines. Consistent with this hypothesis, greater trans amide preferences were found in CDCl₃ for anti isomers en-MetFlp and en-MetHyp (72–78% trans) than for the syn stereoisomers ex-MetFlp and ex-MetHyp (54–67% trans). These, and other, <i>K</i>_T/C results that we report here indicate how substituents on proline analogues can affect amide preferences by pathways other than ring puckering and n→π* overlap and suggest that caution should be exercised in assigning enhanced pyrrolidine C^γ-exo ring puckering based solely on enhanced trans amide preference

Synthesis of Conformationally Constrained 5-Fluoro- and 5-Hydroxymethanopyrrolidines. Ring-Puckered Mimics of <i>Gauche</i>- and <i>Anti</i>-3-Fluoro- and 3-Hydroxypyrrolidines

N-Acetylmethanopyrrolidine methyl ester and its four 5-syn/anti-fluoro and hydroxy derivatives have been synthesized from 2-azabicyclo[2.2.0]hex-5-ene, a 1,2-dihydropyridine photoproduct. These conformationally constrained mimics of idealized Cβ-gauche and Cβ-anti conformers of pyrrolidines were prepared in order to determine the inherent bridge bias and subsequent heteroatom substituent effects upon trans/cis amide preferences. The bridgehead position and also the presence of gauche(syn)/anti-5-fluoro or 5-hydroxy substituents have minimal influence upon the KT/C values of N-acetylamide conformers in both CDCl3 (43–54% trans) and D2O (53–58% trans). O-Benzoylation enhances the trans amide preferences in CDCl3 (65% for a syn-OBz, 61% for an anti-OBz) but has minimal effect in D2O. The synthetic methods developed for N-BOC-methanopyrrolidines should prove useful in the synthesis of more complex derivatives containing α-ester substituents. The KT/C results obtained in this study establish baseline amide preferences that will enable determination of contributions of α-ester substituents to trans-amide preferences in methanoprolines

Synthesis of Conformationally Constrained 5-Fluoro- and 5-Hydroxymethanopyrrolidines. Ring-Puckered Mimics of <i>Gauche</i>- and <i>Anti</i>-3-Fluoro- and 3-Hydroxypyrrolidines

N-Acetylmethanopyrrolidine methyl ester and its four 5-syn/anti-fluoro and hydroxy derivatives have been synthesized from 2-azabicyclo[2.2.0]hex-5-ene, a 1,2-dihydropyridine photoproduct. These conformationally constrained mimics of idealized Cβ-gauche and Cβ-anti conformers of pyrrolidines were prepared in order to determine the inherent bridge bias and subsequent heteroatom substituent effects upon trans/cis amide preferences. The bridgehead position and also the presence of gauche(syn)/anti-5-fluoro or 5-hydroxy substituents have minimal influence upon the KT/C values of N-acetylamide conformers in both CDCl3 (43–54% trans) and D2O (53–58% trans). O-Benzoylation enhances the trans amide preferences in CDCl3 (65% for a syn-OBz, 61% for an anti-OBz) but has minimal effect in D2O. The synthetic methods developed for N-BOC-methanopyrrolidines should prove useful in the synthesis of more complex derivatives containing α-ester substituents. The KT/C results obtained in this study establish baseline amide preferences that will enable determination of contributions of α-ester substituents to trans-amide preferences in methanoprolines

Synthesis of Conformationally Constrained 5-Fluoro- and 5-Hydroxymethanopyrrolidines. Ring-Puckered Mimics of <i>Gauche</i>- and <i>Anti</i>-3-Fluoro- and 3-Hydroxypyrrolidines

N-Acetylmethanopyrrolidine methyl ester and its four 5-syn/anti-fluoro and hydroxy derivatives have been synthesized from 2-azabicyclo[2.2.0]hex-5-ene, a 1,2-dihydropyridine photoproduct. These conformationally constrained mimics of idealized Cβ-gauche and Cβ-anti conformers of pyrrolidines were prepared in order to determine the inherent bridge bias and subsequent heteroatom substituent effects upon trans/cis amide preferences. The bridgehead position and also the presence of gauche(syn)/anti-5-fluoro or 5-hydroxy substituents have minimal influence upon the KT/C values of N-acetylamide conformers in both CDCl3 (43–54% trans) and D2O (53–58% trans). O-Benzoylation enhances the trans amide preferences in CDCl3 (65% for a syn-OBz, 61% for an anti-OBz) but has minimal effect in D2O. The synthetic methods developed for N-BOC-methanopyrrolidines should prove useful in the synthesis of more complex derivatives containing α-ester substituents. The KT/C results obtained in this study establish baseline amide preferences that will enable determination of contributions of α-ester substituents to trans-amide preferences in methanoprolines

Synthesis of Conformationally Constrained 5-Fluoro- and 5-Hydroxymethanopyrrolidines. Ring-Puckered Mimics of <i>Gauche</i>- and <i>Anti</i>-3-Fluoro- and 3-Hydroxypyrrolidines

N-Acetylmethanopyrrolidine methyl ester and its four 5-syn/anti-fluoro and hydroxy derivatives have been synthesized from 2-azabicyclo[2.2.0]hex-5-ene, a 1,2-dihydropyridine photoproduct. These conformationally constrained mimics of idealized Cβ-gauche and Cβ-anti conformers of pyrrolidines were prepared in order to determine the inherent bridge bias and subsequent heteroatom substituent effects upon trans/cis amide preferences. The bridgehead position and also the presence of gauche(syn)/anti-5-fluoro or 5-hydroxy substituents have minimal influence upon the KT/C values of N-acetylamide conformers in both CDCl3 (43–54% trans) and D2O (53–58% trans). O-Benzoylation enhances the trans amide preferences in CDCl3 (65% for a syn-OBz, 61% for an anti-OBz) but has minimal effect in D2O. The synthetic methods developed for N-BOC-methanopyrrolidines should prove useful in the synthesis of more complex derivatives containing α-ester substituents. The KT/C results obtained in this study establish baseline amide preferences that will enable determination of contributions of α-ester substituents to trans-amide preferences in methanoprolines