Isolation and structural determination of non-racemic tertiary cathinone derivatives

The racemic tertiary cathinones N,N-dimethylcathinone (1), N,N-diethylcathinone (2) and 2-(1-pyrrolidinyl)-propiophenone (3) have been prepared in reasonable yield and characterized using NMR and mass spectroscopy. HPLC indicates that these compounds are isolated as the anticipated racemic mixture. These can then be co-crystallized with (+)-O,O′-di-p-toluoyl-D-tartaric, (+)-O,O′-dibenzoyl-D-tartaric and (−)-O,O′-dibenzoyl-L-tartaric acids giving the single enantiomers S and R respectively of 1, 2 and 3, in the presence of sodium hydroxide through a dynamic kinetic resolution. X-ray structural determination confirmed the enantioselectivity. The free amines could be obtained following basification and extraction. In methanol these are reasonably stable for the period of several hours, and their identity was confirmed by HPLC and CD spectroscopy

Ruthenium ion catalysed C–C bond activation in lignin model compounds – towards lignin depolymerisation

Lignin is the most abundant renewable feedstock to produce aromatic chemicals, however its depolymerisation involves the breaking of several C–O and C–C inter-unit linkages that connect smaller aromatic units that are present in lignin. Several strategies have been reported for the cleavage of the C–O inter-unit linkages in lignin. However, till today, only a few methodologies have been reported for the effective breaking or the conversion of the recalcitrant C–C inter unit linkages in lignin. Here we report the ruthenium ion catalysed oxidative methodology as an effective system to activate or convert the most recalcitrant inter unit linkages such as β-5 and 5–5′ present in lignin. Initially, we used biphenyl as a model compound to study the effectiveness of the RICO methodology to activate the 5–5′ C–C linkage. After 4 h reaction at 22 °C, we achieved a 30% conversion with 75% selectivity towards benzoic acid and phenyl glyoxal as the minor product. To the best of our knowledge this is the first ever oxidative activation of the C–C bond that connects the two phenyl rings in biphenyl. DFT calculation revealed that the RuO4 forms a [3 + 2] adduct with one of the aromatic C–C bonds resulting in the opening of the phenyl ring. Biphenyl conversion could be increased by increasing the amount of oxidant; however, this is accompanied by a reduction in the carbon balance because of the formation of CO2 and other unknown products. We extended this RICO methodology for the oxidative depolymerisation of lignin model hexamer containing β-5, 5–5′ and β-O-4 linkages. Qualitative and quantitative analyses of the reaction mixture were done using 1H, 13C NMR spectroscopy methods along with GC-MS and Gel Permeation Chromatographic (GPC) methods. Advanced 2D NMR spectroscopic methods such as HSQC, HMBC and 31P NMR spectroscopy after phosphitylation of the mixture were employed to quantitatively analyse the conversion of the β-5, 5–5′ and β-O-4 linkages and to identify the products. After 30 min, >90% of the 5–5′ and linkages and >80% of the β-5′ are converted with this methodology. This is the first report on the conversion of the 5–5′ linkage in lignin model hexamer

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Biotransformation of substituted pyridines with dioxygenase-containing microorganisms

A series of 2-, 3- and 4-substituted pyridines was metabolised using the mutant soil bacterium Pseudomonas putida UV4 which contains a toluene dioxygenase ( TDO) enzyme. The regioselectivity of the biotransformation in each case was determined by the position of the substituent. 4-Alkylpyridines were hydroxylated exclusively on the ring to give the corresponding 4-substituted 3- hydroxypyridines, while 3- alkylpyridines were hydroxylated stereoselectively on C-1 of the alkyl group with no evidence of ring hydroxylation. 2-Alkylpyridines gave both ring and side-chain hydroxylation products. Choro- and bromo-substituted pyridines, and pyridine itself, while being poor substrates for P. putida UV4, were converted to some extent to the corresponding 3- hydroxypyridines. These unoptimised biotransformations are rare examples of the direct enzyme-catalysed oxidation of pyridine rings and provide a novel synthetic method for the preparation of substituted pyridinols. Evidence for the involvement of the same TDO enzyme in both ring and side-chain hydroxylation pathways was obtained using a recombinant strain of Escherichia coli (pKST11) containing a cloned gene for TDO. The observed stereoselectivity of the side-chain hydroxylation process in P. putida UV4 was complicated by the action of an alcohol dehydrogenase enzyme in the organism which slowly leads to epimerisation of the initial (R)-alcohol bioproducts by dehydrogenation to the corresponding ketones followed by stereoselective reduction to the (S)-alcohols

Biocatalytic conversion of lignin model oligomer using a laccase-mediator system

The use of the laccase enzyme from the fungus Trametes versicolor, coupled with the mediator 1-hydroxybenzotriazole (1-HBT) has been shown to be effective for the biocatalytic conversion of a hexameric lignin model compound containing three of the most common linkages found in native lignin. Cleavage of the model takes place over a 24 hours period predominantly at the β-O-4 ether linkage to give a previously known β-5 dimer intermediate which in turn was rapidly consumed to further degradation products. There is also mass spectrometric evidence of repolymerisation of the β-5 dimer and other degradation intermediates to form higher oligomers. Mechanistic pathways to account for the major catalytic processes are proposed

Platform-specific restrictions on concurrency in model checking of Java programs

The main limitation of software model checking is that, due to state explosion, it does not scale to real-world multi-threaded programs. One of the reasons is that current software model checkers adhere to full semantics of programming languages, which are based on very permissive models of concurrency. Current runtime platforms for programs, however, restrict concurrency in various ways - it is visible especially in the case of critical embedded systems, which typically involve only a single processor and use a threading model based on limited preemption. In this paper, we present a technique for addressing state explosion in model checking of Java programs for embedded systems, which exploits restrictions on concurrency common to current Java platforms for such systems. We have implemented the technique in Java PathFinder and performed a number of experiments on Purdue Collision Detector, which is a non-trivial multi-threaded Java program. Results of experiments show that use of the restrictions on concurrency in model checking with Java PathFinder reduces the state space size by an order of magnitude and also reduces the time needed to discover errors in Java programs

CCDC 943403: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures