Chemical Science Blog

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is responsible for the deaths of millions of people every year, while one third of the world’s population is infected with a dormant form of the bacteria. Researchers propose that better understanding of how the immune system copes with M. tuberculosis infection could aid the design of new vaccines to limit bacteria growth, and to eradicate any latent forms. Ac₂SGL (1) is a sulfoglycolipid found in the outer membrane of M. tuberculosis which has been implicated in the modulation of TB growth and development, and as such, has potential for use in a new vaccine.

The first asymmetric total synthesis of Ac₂SGL has been reported by Prof. Minnaard at the Stratingh Institute for Chemistry, University of Groningen. This elegant work resulted from a large international collaboration between researchers from the Stratingh Institute and the University of Toulouse, as well as a number of experimental immunologists from University Hospital Basel and the Singapore Immunology Network at the Agency for Science, Technology and Research (A*STAR).

To synthesise the hydroxyphthioceranic acid side chain, the researchers utilised an efficient and highly stereoselective iterative process for the construction of the 1,3-syn substituted fatty acid. The sequence was comprised of reduction, Horner–Wadsworth–Emmons olefination, and copper-catalysed asymmetric 1,4-addition (shown below).

The side chain was completed using copper-catalysed asymmetric allylic substitution and platinum-catalysed diboration/oxidation to install the requisite functionality with excellent diastereoselectivity. This hydroxyphthioceranic acid residue was appended to the disaccharide trehalose. Finally, a regioselective sulfonation at the 2′-position completed the total synthesis.

The biological activity of the synthesised Ac₂SGL was investigated, and found to be comparable with naturally isolated material. The researchers undertook modelling studies which shed light on Ac₂SGL’s binding interactions and 3D conformation. This information, and the efficient total synthesis, facilitates further investigation into the use of Ac₂SGL as a TB vaccine.

Read this ‘HOT’ Chemical Science article today:

Total synthesis, stereochemical elucidation and biological evaluation of Ac₂SGL; a 1,3-methyl branched sulfoglycolipid from Mycobacterium tuberculosis

Danny Geerdink, Bjorn ter Horst, Marco Lepore, Lucia Mori, Germain Puzo, Anna K. H. Hirsch, Martine Gilleron, Gennaro de Libero and Adriaan J. Minnaard.

Chem. Sci., 2013, DOI: 10.1039/C2SC21620E

Polyacetylene and its derivatives are a group of novel π-conjugating polymers. They have unique electronic and conductive properties and have potential use as future important functional materials. 

Scientists in the US have synthesised a new catalyst to polymerise both mono and di-substituted acetylenes, and the first tetra-anionic pincer-type ligand. This ‘HOT’ paper also presents evidence for a new reaction: a reductive alkylidyne migratory insertion into a metal-arene bond (the terminal carbene disappears upon addition of alkyne).

Read this ‘HOT’ Chemical Science article today:

Compelling mechanistic data and identification of the active species in tungsten-catalyzed alkyne polymerizations: conversion of a trianionic pincer into a new tetraanionic pincer-type ligand
Kevin P McGowan, Matthew E O’Reilly, Ion Ghiviriga, Khalil A Abboud and Adam Steven Veige
Chem. Sci., 2012, DOI: 10.1039/C2SC21750C

Scientists in Germany have engineered peptide domains with altered substrate specificities, which leads the way for designer templates to make new bioactive products.

The group have studied hormaomycin, a structurally unusual antibiotic peptide, which is biosynthesized by a bacterial nonribosomal peptide synthetase (NRPS). Analysing amino acid residues of hormaomycin had previously revealed that the NRPS adenylation (A) domains naturally recombine during evolution. This inspired the team to create A domains with altered substrates, which in turn has uncovered new information about the NRPS pathway and suggests new strategies in peptide engineering.

Biosynthetic megaenzymes, such as NRPS, are currently of biomedical interest, as they produce a large number of bioactive metabolites via an assembly mechanism, which shows potential for artificial engineering. Nonribosomal peptides have many clinical applications, including antibiotics, antitumour agents and antifungals.

A significant advantage of this evolution-based engineering is that it requires no insight into protein structures, so while not effective for all NRPS systems, the experimental ease of this method makes it a useful addition to engineering techniques.

Read this ‘HOT’ article today:

Evolution-guided engineering of nonribosomal peptide synthetase adenylation domains
Max Crüsemann, Christoph Kohlhaas and Jörn Piel
Chem. Sci., 2012, DOI: 10.1039/C2SC21722H

Nafion (a perfluorosulfonic acid membrane) is widely used in fuel cells to conduct protons, but Nafion membranes are prone to rapid dehydration at low humidity, which results in a loss of conductivity.

To overcome this problem, scientists in China have made a metal-organic framework (MOF) containing protonated tertiary amines as intrinsic proton carriers and hydrogen-bonding chains as proton-conducting pathways.

A series of composite membranes with different contents of MOF crystals were prepared by blending MOF submicrorods with a polymer for the exploration of further applications of MOFs in fuel cells under low humidity. The MOFs displayed low-humidity proton conductivity.

Read this interesting article hot off the press:

From Metal-Organic Framework (MOF) to MOF/Polymer Composite Membrane: Enhancement of Low-Humidity Proton Conductivity
Xiao Qiang Liang , Feng Zhang , Wei Feng , Xiaoqin Zou , Chengji Zhao , Hui Na , Cong Liu , Guangshan Zhu and Fuxing Sun
Chem. Sci., 2012, DOI: 10.1039/C2SC21927A

Scientists in China have used zeolite-coated mesh films for gravity-driven oil-water separation.

The superhydrophilicity and underwater superoleophobicity of the zeolite’s surface allow the highly efficient separation of various oils.

Unlike other oil-water separation membranes based on superhydrophilic and superoleophobic organic layers, the zeolite inorganic films are corrosion-resistant, which makes them ideal candidates for a range of applications such as an oil retention barrier in industrial outlet sewer pipes, oil fences for oil spill accidents and separation of domestic waste oil.

 Read the ‘HOT’ Chemical Science article:

Zeolite-coated mesh film for efficient oil-water separation
Qiang Wen , Jiancheng Di , Lei Jiang , Jihong Yu and Ruren Xu
Chem. Sci., 2012, DOI: 10.1039/C2SC21772D