Organic & Biomolecular Chemistry Blog

A recent communication in Organic and Biomolecular Chemistry reports the synthesis of a new reagent for the introduction of alkynes into proteins; a key step for click bioconjugation. The new diazonium reagent was prepared in a one-pot synthesis from commercially available 4-ethynylaniline.

Having optimized bioconjugation in a tyrosine containing small molecule, the new diazonium reagent was then used to covalently label proteins. Fluorescence labelling of protein surface tyrosine residues was achieved under mild conditions (pH 8.0) by reaction of the protein with the diazonium reagent and subsequent reaction with an azide-containing fluorescent compound. The new diazonium reagent was also used to achieve protein PEGylation; a strategy that could be employed to improve protein stability and reduce immunogenicity.

The new diazonium reagent can facilitate bioconjugation in a range of proteins and could be a useful addition to the biochemist’s toolbox.

Read the full article:
An efficient reagent for covalent introduction of alkynes into proteins
Jie Zhang, Dejun Ma, Dawei Du, Zhen Xi and Long Yi
Org. Biomol. Chem., 2014, DOI: 10.1039/C4OB01873G

The following Organic & Biomolecular Chemistry articles have all been recommened by the reviewers of the articles as being particularly interesting or particularly significant research. These have all been made free to access until 30th November. The order they appear in the list holds no special meaning or ranking.

Design strategies for bioorthogonal smart probes
Peyton Shieh and Carolyn R. Bertozzi
DOI: 10.1039/C4OB01632G, Review Article

Stereoselective intermolecular [2 + 2]-photocycloaddition reactions of maleic anhydride: stereocontrolled and regiocontrolled access to 1,2,3-trifunctionalized cyclobutanes
Florian Hernvann, Gloria Rasore, Valérie Declerck and David J. Aitken
DOI: 10.1039/C4OB01383B, Paper

Towards novel efficient and stable nuclear import signals: synthesis and properties of trimethylguanosine cap analogs modified within the 5′,5′-triphosphate bridge
Malgorzata Zytek, Joanna Kowalska, Maciej Lukaszewicz, Blazej A. Wojtczak, Joanna Zuberek, Aleksandra Ferenc-Mrozek, Edward Darzynkiewicz, Anna Niedzwiecka and Jacek Jemielity
DOI: 10.1039/C4OB01579G, Paper

Catalytic asymmetric synthesis of the pentacyclic core of (−)-nakadomarin A via oxazolidine as an iminium cation equivalent
Nobuya Tsuji, Michael Stadler, Naoya Kazumi, Tsubasa Inokuma, Yusuke Kobayashi and Yoshiji Takemoto
DOI: 10.1039/C4OB01678E, Communication

Short and efficient synthesis of fluorinated δ-lactams
Thomas J. Cogswell, Craig S. Donald, De-Liang Long and Rodolfo Marquez
DOI: 10.1039/C4OB01547A, Paper

An efficient route to synthesize isatins by metal-free, iodine-catalyzed sequential C(sp3)–H oxidation and intramolecular C–N bond formation of 2′-aminoacetophenones
Venkatachalam Rajeshkumar, Selvaraj Chandrasekar and Govindasamy Sekar
DOI: 10.1039/C4OB01564A, Paper

5-Nitroindole oligonucleotides with alkynyl side chains: universal base pairing, triple bond hydration and properties of pyrene “click” adducts
Sachin A. Ingale, Peter Leonard, Haozhe Yang and Frank Seela
DOI: 10.1039/C4OB01478B, Paper

Cross-strand histidine–aromatic interactions enhance acyl-transfer rates in beta-hairpin peptide catalysts
M. Matsumoto, S. J. Lee, M. R. Gagné and M. L. Waters
DOI: 10.1039/C4OB01754D, Paper

The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes
Stephen G. Davies, Ai M. Fletcher, Emma M. Foster, Ian T. T. Houlsby, Paul M. Roberts, Thomas M. Schofield and James E. Thomson
DOI: 10.1039/C4OB01737D, Paper

Organocatalytic Michael addition–lactonisation of carboxylic acids using α,β-unsaturated trichloromethyl ketones as α,β-unsaturated ester equivalents
Louis C. Morrill, Daniel G. Stark, James E. Taylor, Siobhan R. Smith, James A. Squires, Agathe C. A. D’Hollander, Carmen Simal, Peter Shapland, Timothy J. C. O’Riordan and Andrew D. Smith
DOI: 10.1039/C4OB01788A, Paper

The Ugi reaction was one of the very first multicomponent reactions exploited to develop chemical libraries, which further extended to combinatorial, solid phase and flow synthesis for evolving new lead structures of active agents. Implementing the Ugi reaction in combination with other organic reactions enlarges the chemical diversity of possible products.

Researchers at Vrije University Brussel, led by Steven Ballet, have made a step forward by executing a one-pot Ugi-Huisgen tandem reaction and found an alternative high atom economy pathway for the synthesis of conformationally constrained, amino-triazoloazepinone-containing di- and tripeptides.

Strategically, they have used an unconventional azide containing acid, and alkyne amine along with traditional aldehydes and isocyanides. By using equimolar reactants with very mild reaction conditions, they were able to observe total conversion to the linear Ugi-compounds equipped with azide and alkyne functionality. Furthermore, they have cyclised the resulting compounds into the respective triazoles, by performing a catalyst-free Huisgen cycloaddition reaction in a sealed tube.

Variation in substitution patterns and tolerance of a large array of aldehydes in this methodology will open a new avenue for the synthesis of various building blocks to be used in peptidomimetics with a wide range of applications.

Find out more in their Communication:

Efficient synthesis of conformationally constrained, amino-triazoloazepinone-containing di- and tripeptides via a one-pot Ugi–Huisgen tandem reaction
T. M. A. Barlow, M. Jida, D. Tourwéa and S. Ballet
DOI: 10.1039/C4OB01381F

Check out the following HOT articles, as recommened by the reviewers of the articles. These have all been made free to access until 20th October:

Estimating the shape and size of supramolecular assemblies by variable temperature diffusion ordered spectroscopy
Benjamin M. Schulze, Davita L. Watkins, Jing Zhang, Ion Ghiviriga and Ronald K. Castellano
DOI: 10.1039/C4OB01373E, Communication

Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification
James J. Sahn, Brett A. Granger and Stephen F. Martin
DOI: 10.1039/C4OB00835A, Review Article
From themed collection In Celebration of Richard Taylor’s 65^th Birthday

Development and mechanistic studies of an optimized receptor for trimethyllysine using iterative redesign by dynamic combinatorial chemistry
Nicholas K. Pinkin and Marcey L. Waters
DOI: 10.1039/C4OB01249F, Paper

Modulation of DNA–polyamide interaction by β-alanine substitutions: a study of positional effects on binding affinity, kinetics and thermodynamics
Shuo Wang, Karl Aston, Kevin J. Koeller, G. Davis Harris, Nigam P. Rath, James K. Bashkin and W. David Wilson
DOI: 10.1039/C4OB01456A, Paper

Iridium-catalyzed C–H borylation of pyridines
Scott A. Sadler, Hazmi Tajuddin, Ibraheem A. I. Mkhalid, Andrei S. Batsanov, David Albesa-Jove, Man Sing Cheung, Aoife C. Maxwell, Lena Shukla, Bryan Roberts, David C. Blakemore, Zhenyang Lin, Todd B. Marder and Patrick G. Steel
DOI: 10.1039/C4OB01565G, Paper

Efficient synthesis of conformationally constrained, amino-triazoloazepinone-containing di- and tripeptides via a one-pot Ugi–Huisgen tandem reaction
T. M. A. Barlow, M. Jida, D. Tourwé and S. Ballet
DOI: 10.1039/C4OB01381F, Communication

Influence of B-ring modifications on proton affinity, transmembrane anion transport and anti-cancer properties of synthetic prodigiosenes
Estelle Marchal, Soumya Rastogi, Alison Thompson and Jeffery T. Davis
DOI: 10.1039/C4OB01399A, Paper

Catalytic amide allylation of α-ketoesters: extremely high enantioselective synthesis of ester functionalised α-methylene-γ-butyrolactones
Masaki Takahashi, Yusuke Murata, Masahiro Ishida, Fumitoshi Yagishita, Masami Sakamoto, Tetsuya Sengoku and Hidemi Yoda
DOI: 10.1039/C4OB01508H, Communication

Recent developments in transition metal-catalysed spiroketalisation
Rachelle Quach, Daniel F. Chorley and Margaret A. Brimble
DOI: 10.1039/C4OB01325E, Perspective

Non-isoprenoid polyene natural products – structures and synthetic strategies
Katrina S. Madden, Fathia A. Mosa and Andrew Whiting
DOI: 10.1039/C4OB01337A, Review Article

A Lewis acid-mediated conformational switch
Peter C. Knipe, Hannah Lingard, Ian M. Jones, Sam Thompson and Andrew D. Hamilton
DOI: 10.1039/C4OB01556H, Paper