Fast prediction of distances between synthetic routes with deep learning

We expand the recent work on clustering of synthetic routes and train a deep learning model to predict the distances between arbitrary routes. The model is based on an long short-term memory (LSTM) representation of a synthetic route and is trained as a twin network to reproduce the tree edit distance (TED) between two routes. The ML approach is approximately two orders of magnitude faster than the TED approach and enables clustering many more routes from a retrosynthesis route prediction. The clusters have a high degree of similarity to the clusters given by the TED-based approach and are accordingly intuitive and explainable. We provide the developed model as open-source.

A Potentially Limitless Chiral Pool via Conglomerate Crystallisation: Unidentified Spontaneous Resolution in the CSD.

Conglomerate crystallisation is the behaviour responsible for spontaneous resolution and the discovery of molecular chirality by Pasteur. The phenomenon of conglomerate crystallisation of chiral organic molecules has been left largely undocumented and offers synthetic chemists a potential new chiral pool not reliant on biological systems to supply stereochemical information. While other crystallographic behaviours can be interrogated by automated searching, conglomerate crystallisations are not identified within the Cambridge Structural Database (CSD) and are therefore not accessible by conventional means. By conducting a manual search of the CSD, a list of over 1,700 chiral species capable of conglomerate crystallisation was curated by inspection of the synthetic routes described in each publication. The majority of these are produced by synthetic chemists who seldom note and rarely exploit the implications this phenomenon can have on the enantioenrichment of their crystalline materials. We propose that this list represents a limitless chiral pool which will continually grow in size as more conglomerate crystals are synthesised and recorded.

Synthetic Studies with the Brevicidine and Laterocidine Lipopeptide Antibiotics Including Analogues with Enhanced Properties and in vivo Efficacy

Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, and a lipidated N-terminus, these lipopeptides exhibit potent and selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine and laterocidine accessible by fermentation of the producing microorganisms, synthetic routes to these lipopeptides present an attractive alternative. We here report the convenient solid-phase syntheses of both brevicidine and laterocidine and confirm their potent anti-Gram-negative activities. The synthetic routes developed also provide convenient access to novel structural analogues of both brevicidine and laterocidine that display improved hydrolytic stability while maintaining potent antibacterial activity in both in vitro assay and in vivo infection models.

Directed Evolution of a Ketone Synthase for Efficient and Highly Selective Functionalization of Internal Alkenes by Accessing Reactive Carbocation Intermediates

The direct regioselective oxidation of internal alkenes to ketones could simplify synthetic routes and solve a longstanding challenge in synthesis. This reaction is of particular importance because ketones are predominant moieties in valuable products as well as crucial intermediates in synthesis. Here we report the directed evolution of a ketone synthase that oxidizes internal alkenes directly to ketones with several thousand turnovers. The evolved ketone synthase benefits from more than a dozen crucial mutations, most of them distal to the active site. Computational analysis reveals that all these mutations collaborate to facilitate the formation of a highly reactive carbocation intermediate by generating a confined, rigid and preorganized active site through an enhanced dynamical network. The evolved ketone synthase fully exploits a catalytic cycle that has largely eluded small molecule catalysis and consequently enables various challenging functionalization reactions of internal alkenes. This includes the first catalytic, enantioselective oxidation of internal alkenes to ketones, as well as the formal asymmetric hydration and hydroamination of unactivated internal alkenes in combination with other biocatalysts.

Manganese (I)-Catalyzed Access to 1,2-Bisphosphine Ligands

Chiral bisphosphine ligands are of key importance in transition-metal-catalyzed asymmetric synthesis of optically active products. However, the transition metals typically used are scarce and expensive noble metals, while the synthetic routes...

Photochemical and Electrochemical C–N Borylation of Arylhydrazines

The C–N borylation of arylhydrazine hydrochlorides with bis(pinacolato)diboron was achieved under photochemical and electrochemical conditions, respectively. This novel and scalable transformation provides two efficient and mild transition-metal-free synthetic routes towards...

Multivariate sodalite Zeolitic Imidazolate frameworks: a direct solvent-free synthesis

Different mixed-ligand Zeolitic Imidazolate Frameworks (ZIFs) with sodalite topology, i.e. isoreticular to ZIF-8, unachievable by conventional synthetic routes, have been prepared using a solvent-free methodology. In particular, the versatility of...

Poly(1-halogen-2-phenylacetylenes) Containing Tetraphenylethene Unit: Polymer Synthesis, Unique Emission Behaviours and Application in Explosive Detection

Pd-based catalysts have shown high activity in the polymerization of 1-chloro-2-phenylacetylene monomers in mild condition, but it is still a challenge to find synthetic routes to the polymers with high...

Green Nanomaterials for Photocatalytic Degradation of Toxic Organic Compounds

In recent years, nanomaterials as photocatalysts have gained much popularity for the removal of organic pollutants from tainted water using photodegradation, since the available chemical, physical, and biological methods often are time consuming, involve high cost and dumping complications, sometimes posing serious threat to both human health and environmental elements. Use of nanomaterials is less expensive and does not, in general, form aggregated macromolecules. In addition, nanotechnology for waste-water treatment demolishes or alters the risky chemical wastes to harmless end products like H2O and CO2. Nanomaterials synthesized from natural resources or prepared using green synthetic routes are receiving surge of interest as our consciousness to ecological environment and safety rises. ‘Green’ materials of this kind might also show unique strength features and exceptional biodegradability, along with their other notable advantageous properties like minimum threat to environment, efficient recyclablity and low cost compared to synthetic nanomaterials. Such green nanomaterials can also serve as nanocatalysts to treat toxic organic pollutants in a safer way, including photodegradation to less or non-toxic products. This article reviews latest developments on the synthesis of some promising green nanomaterials aiming towards their efficient uses as photocatalysts for degradation of organic pollutants. Strategies to find new green materials as photocatalysts by modification of technologies, and development of novel methodologies for safer treatment of organic pollutants will also be discussed.

Synthesis, Characterization, and Spectroscopic Studies of Bis-(meso-4-methoxyphenyl)-Benziporphyrin and Its Pd-Metal Complex

Benziporphyrin systems are widely explored, yet alternative improved synthetic routes towards these systems are needed. Here, a fairly and efficient synthesis of the free base and its metal complex is well designed. Dimethoxybenzene dicarbinol intermediate was prepared in excellent yields by reacting 4-methoxyphenylmagnesium bromide with isophthaladehyde in diethyl ether. Reaction with equivalent pyrrole and pentafluorobenzaldehyde in the presence of trifluoroacetic acid (TFA), followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), provided good yields of bis-(meso-4-methoxyphenyl)-benziporphyrin. Metalation of the free base was performed using palladium(II) acetate salt in acetonitrile. All intermediates and the final products are fully characterized using NMR, HMRS, and UV-Vis spectroscopies and briefly discussed.