Chemical Science Blog

A strategy for regiochemical reversal of reductive macrocyclisations of aldehydes and terminal alkynes has been developed by US researchers. Using an advanced synthetic intermediate directed towards the methymycin/neomethymycin class of macrolides, selective endocyclisation provides the natural twelve-membered ring series, whereas ligand alteration enables selective exocyclisation to provide access to the  unnatural eleven-membered ring series. The twelve-membered ring adduct was converted to 10- deoxymethynolide, completing an efficient total synthesis of this natural product.

Reference:
Nickel-Catalyzed Regiodivergent Approach to Macrolide Motifs
A-R Shareef, D H Sherman and J Montgomery, Chem. Sci., 2012
DOI: 10.1039/c2sc00866a

A mild and efficient procedure for the oxidative alkynylation of N- and P-based nucleophiles has been devised by scientists in France to make ynamides and alkynylphosphonates. These versatile alkynes add functionality to organic molecules and are used in medicinal chemistry and materials science. The heteroatom polarises the triple bond, allowing for highly regio- and stereoselective transformations. An advantage of the method is that it does not require a base, thermal activation, an inert atmosphere or expensive chemicals.

Reference:
Click-Alkynylation of N- and P- Nucleophiles by Oxidative Cross-Coupling with Alkynylcopper Reagents: A General Synthesis of Ynamides and Alkynylphosphonates.
K Jouvin, J Heimburger and G Evano, Chem. Sci., 2012
DOI: 10.1039/c2sc00842d

High nucleophilic reactivity and functional group tolerance are opposing properties of organometallic compounds. While organolithium compounds are highly nucleophilic so react with most electrophiles, organosilicon compounds are on the low reactivity end of the nucleophilicity scale. They tolerate numerous electrophilic functional groups and often require (Lewis) base activation to react.

Organoboron compounds, which are key intermediates in organic synthesis, are positioned in between. While some of them undergo non-catalysed C–C bond forming reactions with various electrophiles, others tolerate a variety of functional groups and are most valuable substrates for Pd-catalysed cross couplings (Suzuki–Miyaura reactions).

As it is difficult for the preparative chemist to decide which functional groups are tolerated and which do react with organoboron reagents in the absence of a catalyst, scientists in Germany have established a quantitative reactivity scale for representatives of the most important classes of organoboron reagents and they have applied these data for predicting the feasibility of transition metal free C–C bond forming reactions.

Reference:
Nucleophilicity parameters for designing transition metal-free C-C bond forming reactions of organoboron compounds
G Berionni, B Maji, P Knochel and H Mayr, Chem. Sci., 2012
DOI: 10.1039/c2sc00883a

Scientists in Germany have synthesised the core part of a sugar compound produced by the pathogenic bacteria responsible for meningitis – Neisseria meningitides – which could be used in a vaccine for meningococcal diseases, in particular meningitis B.

Pathogenic bacteria produce a polysaccharide layer, forming a capsule to cloak antigenic proteins on their surface that would otherwise provoke an immune response to destroy the bacteria. Currently available vaccines are based on capsular polysaccharides and provide protection against four major forms of meningitis, but not meningitis B. This is because the capsular polysaccharide for meningitis B resembles carbohydrates present in the central nervous system, so using it in a vaccine risks triggering an immune response against them as well.

Now, Peter Seeberger from the Max Planck Institute of Colloids and Interfaces, Potsdam, and colleagues have made the inner core of the lipopolysaccharide produced by N. meningitides as a safer alternative. The resulting tetrasaccharide consists of Hep (heptose) and Kdo (octulosonic acid) building blocks.

Synthesis of the core tetrasaccharide of Neisseria meningitidis lipopolysaccharide
Total synthesis of the core tetrasaccharide of Neisseria meningitidis lipopolysaccharide, a potential vaccine candidate for meningococcal diseases
You Yang, Christopher E. Martin and Peter H. Seeberger
Chem. Sci., 2012, Advance Article
DOI: 10.1039/C1SC00804H

Read the full story in Chemistry World

Link to journal article

Scientists from the UK have used a molecular capsule to control the reactivity of an organic compound.

A molecule’s reactivity is commonly controlled using protecting group chemistry, in which a certain functional group is blocked to avoid unwanted reactions at that site. However, this can be costly in terms of time and reagents.

Now, Maarten Smulders and Jonathan Nitschke from the University of Cambridge have used a supramolecular cage as a whole-molecule protecting group. An organic molecule can be encapsulated within the cage, preventing its reaction, and addition of a competing guest can then release the molecule and initiate the reaction when required.

The team constructed the cage from four iron units in a tetrahedral arrangement. External sulfonate groups confer water solubility, while the interior of the cage provides a hydrophobic environment to encapsulate organic molecules. Unlike traditional protecting group chemistry, this method relies not on the functionality of the molecule but on its size and shape, providing a complementary protection strategy to those commonly used.

Encapsulation of furan prevents its reaction, but upon addition of benzene as a competing guest, furan is released from the cage and undergoes a Diels-Alder reaction with maleimide

Read the full story in Chemistry World

Link to journal article
Supramolecular control over Diels–Alder reactivity by encapsulation and competitive displacement
Maarten M. J. Smulders and Jonathan R. Nitschke
Chem. Sci., 2012, Advance Article
DOI: 10.1039/C1SC00847A

New guanosine-based gels for use as tissue engineering scaffolds have been made by scientists in the US. The gels can gel aqueous solutions and cell media at physiological salt concentrations. They are also injectable and non-toxic to cells.

Previous gels have had limited use because of poor lifetime stability and the need for specific salt concentrations or pH values that are not physiological. These new gels form helical assemblies rather than the quartet assemblies that are normally found in guanosine gelators. This allows them to form hydrogels at physiological salt concentrations – as low as 0.5wt% in 100mM NaCl.

The researchers acknowledge that there are issues to be addressed, such as the development of gel systems that allow cell adhesion without added gelatine, and studies into the lifetime of the gels in cell media.

Reference:
Toward Potential Supramolecular Tissue Engineering Scaffolds Based on Guanosine Derivatives
L E Buerkle, H A von Recum and S J Rowan, Chem. Sci., 2011
DOI: 10.1039/c1sc00729g

It is possible to induce a pronounced structural reorganisation of a metallasupramolecular cage complex with a very conservative change in solvent polarity, say researchers from Switzerland and Turkey.

Solvent-switchable nanostructures reported so far operate via solvent-induced reduction or stabilisation of non-covalent interactions. This cage switches from octanuclear prismatic in chloroform to tetranuclear in dichloromethane. The key to success here is the incorporation of metallacrown recognition units into flexible nanostructures, which allowed generation of solvent specific bonding pockets.

Reference:
A solvent-responsive coordination cage
B Kilbas, S Mirtschin, R Scopelliti and K Severin, Chem. Sci., 2011
DOI: 10.1039/c1sc00779c

A molecule that can distinguish between structurally similar carboxylic acids and organoboronic acids – a significant analytical challenge – has been made by US researchers. The molecule is a cruciform (cross-shaped).

Identifying compounds with closely related structures like this is important to identify counterfeited, decomposed or compromised pharmaceuticals, food additives and alcoholic beverages. The compound can distinguish between 12 carboxylic acids and nine organoboronic acids. It works by binding to the compounds and giving a different fluorescent signal for each one.

Reference:
Identification of Carboxylic and Organoboronic Acids and Phenols with a Single Benzobisoxazole Fluorophore
J Lim, D Nam and O S Miljanic, Chem. Sci., 2011
DOI: 10.1039/c1sc00610j