Anion recognition using a simple cyclic peptide

The head-to-tail cyclic hexapeptide, [cyclo(Val-Thr)3], was found to bind to a range of anions in DMSO-d6 with higher affinity for tetrahedral oxo-anions than halides. 1H NMR spectroscopy indicated that anion binding results in an overall change in peptide conformation with the binding of both sulphate and selenate leading to similar peptide conformations. In the more competitive solvent mixture of 2:8 v/v H2O/DMSO-d6 this cyclic peptide displayed five-fold stronger binding to sulphate than to selenate.</p

Pseudoprolines as Removable Turn Inducers: Tools for the Cyclization of Small Peptides

The cyclization of small peptides which do not incorporate turn inducers is often difficult. We have developed a method involving the use of removable turn inducers, in the form of pseudoprolines, for the cyclization of difficult peptide sequences. The pseudoprolines induce a cisoid amide bond in the peptide backbone which facilitates cyclization. They are then readily removed to yield a cyclic peptide that does not contain any turn inducers

Pseudoprolines as Removable Turn Inducers: Tools for the Cyclization of Small Peptides

The cyclization of small peptides which do not incorporate turn inducers is often difficult. We have developed a method involving the use of removable turn inducers, in the form of pseudoprolines, for the cyclization of difficult peptide sequences. The pseudoprolines induce a cisoid amide bond in the peptide backbone which facilitates cyclization. They are then readily removed to yield a cyclic peptide that does not contain any turn inducers

<i>N</i>,<i>O</i>-Isopropylidenated Threonines as Tools for Peptide Cyclization: Application to the Synthesis of Mahafacyclin B

The influence of a single N,O-isopropylidenated threonine turn-inducer on the cyclization of a linear heptapeptide precursor to mahafacyclin B has been investigated. Incorporation of an N,O-isopropylidenated threonine more than doubles the head-to-tail cyclization yield. The N,O-isopropylidene grouping is then readily disassembled to give the antimalarial cyclic peptide in high yield

Pseudoprolines as Removable Turn Inducers: Tools for the Cyclization of Small Peptides

The cyclization of small peptides which do not incorporate turn inducers is often difficult. We have developed a method involving the use of removable turn inducers, in the form of pseudoprolines, for the cyclization of difficult peptide sequences. The pseudoprolines induce a cisoid amide bond in the peptide backbone which facilitates cyclization. They are then readily removed to yield a cyclic peptide that does not contain any turn inducers

Synthesis of the Side Chain Cross-Linked Tyrosine Oligomers Dityrosine, Trityrosine, and Pulcherosine

An efficient synthesis of dityrosine and the first syntheses of the tyrosine trimers trityrosine and pulcherosine have been achieved. Protected 3-iodotyrosine underwent tandem Miyaura borylation−Suzuki coupling to give protected dityrosine. The choice of benzyl carbamate, ester, and ether protecting groups enabled a one-step global deprotection to give dityrosine. Suzuki coupling of protected 3,5-diiodotyrosine and tyrosine-3-boronic acid derivatives gave the corresponding trityrosine, but in low yield. However, use of a potassium tyrosine-3-trifluoroborate derivative in place of the corresponding pinacol boronate ester, in combination with protecting group variation, gave protected trityrosine in good yield. Access to pulcherosine was achieved through copper-catalyzed coupling of phenylalanine-4-boronic acid and 4-O-protected dopa derivatives to give an isodityrosine derivative. Selective halogenation followed by Suzuki coupling with the potassium tyrosine-3-trifluoroborate gave protected pulcherosine. Global deprotection of the protected trityrosine and pulcherosine derivatives completed the first syntheses of the corresponding tris-α-amino acids

Total Synthesis of Cyclocitropside A and Its Conversion to Cyclocitropsides B and C via Asparagine Deamidation

The total syntheses of three closely related cyclic peptide natural products, cyclocitropsides A–C, are described. Cyclocitropside A could be readily converted into cyclocitropsides B and C through an asparagine deamidation pathway, indicating that this is a plausible biosynthetic route to these compounds

Synthesis of the Sialic Acid (−)-KDN and Certain Epimers from (−)-3-Dehydroshikimic Acid or (−)-Quinic Acid

(−)-3-Dehydroshikimic acid (3-DHS, 4), a C7-building block now available in large quantity from corn syrup, has been converted into the sialic acid (−)-KDN (3) as well as its C-7- and C-8-epimers. (−)-Quinic acid can be used for the same purpose

Colorimetric and Luminescent Sensors for Chloride: Hydrogen Bonding vs Deprotonation

The synthesis and photophysical properties of four squaramide based fluorescent anion sensors (<b>1</b>–<b>4</b>) are described. These luminescent compounds showed selectivity for Cl^– over various other anions with concomitant changes in both their UV/visible and fluorescence properties upon Cl^– addition, attributed to initial H-bonding followed by NH deprotonation in the presence of excess Cl^–, signaled by a color change. The nature of the electron withdrawing aryl substituents is directly related to the H-bonding ability/acidity of the squaramide protons and can be used to tune the deprotonation behavior

Total Synthesis of Microcin B17 <i>via</i> a Fragment Condensation Approach

The total synthesis of the 43 amino acid antibacterial peptide Microcin B17 (MccB17) is described. The natural product was synthesized via a convergent approach from a heterocycle-derived peptide and peptide thioester fragments prepared via Fmoc-strategy solid phase peptide synthesis (SPPS). Final assembly was achieved in an efficient manner using two Ag(I)-assisted peptide ligation reactions to afford MccB17 in excellent overall yield