The catalyzed hydroboration of vinyl arenes was carried out using pinacol borane instead of catechol borane, as the former reagent and the product boronates are significantly easier to handle. By careful choice of catalyst, either the branched or the linear product can be obtained in greater than 96% selectivity. Interestingly, common ligands such as BINAP and Josiphos give opposite asymmetric induction with pinacol borane as compared with catechol borane, while P,N-ligands such as Quinap gave the same sense of induction. The hydroboration of 6-methoxynaphthalene proceeded with the greatest regio- (95:5) and enantioselectivity (94:6) of all vinyl arenes examined. The hydroboration product was then employed in a concise synthesis of the nonsteroidal antiinflammatory agent, Naproxen.

Any substituent does it: The hydroboration of vinyl arenes with pinacol borane (HBPin) and cationic rhodium complexes selectively placed the boron proximal to the aryl rather than phenyl ring, regardless of whether this ring bears electron‐donating or electron‐withdrawing substituents. In competition experiments between styrene and various vinyl arenes, preferential hydroboration also occured at the substituted arene (see scheme). Hammett plots indicate a break in the mechanism.

Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the MICs of closthioamide to be 0.008 to 0.5 mg/liter for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae.

Background  A key focus of synthetic biology is to develop microbial or cell-free based biobased routes to value-added chemicals such as fragrances. Originally, we developed the EcoFlex system, a Golden Gate toolkit, to study genes/pathways flexibly using Escherichia coli heterologous expression. In this current work, we sought to use EcoFlex to optimise a synthetic raspberry ketone biosynthetic pathway. Raspberry ketone is a high-value (~ £20,000 kg−1) fine chemical farmed from raspberry (Rubeus rubrum) fruit. Results  By applying a synthetic biology led design-build-test-learn cycle approach, we refactor the raspberry ketone pathway from a low level of productivity (0.2 mg/L), to achieve a 65-fold (12.9 mg/L) improvement in production. We perform this optimisation at the prototype level (using microtiter plate cultures) with E. coli DH10β, as a routine cloning host. The use of E. coli DH10β facilitates the Golden Gate cloning process for the screening of combinatorial libraries. In addition, we also newly establish a novel colour-based phenotypic screen to identify productive clones quickly from solid/liquid culture. Conclusions  Our findings provide a stable raspberry ketone pathway that relies upon a natural feedstock (L-tyrosine) and uses only constitutive promoters to control gene expression. In conclusion we demonstrate the capability of EcoFlex for fine-tuning a model fine chemical pathway and provide a range of newly characterised promoter tools gene expression in E. coli.

22Cell-free synthetic biochemistry provides a green solution to replace traditional 23 petroleum or agricultural based methods for production of fine chemicals. 4-(4-24 hydroxyphenyl)-butan-2-one, also known as raspberry ketone, is the major fragrance 25 component of raspberry fruit and is utilised as a natural additive in the food and 26 sports industry. Current industrial processing standards involve chemical extraction 27with a yield of 1-4 mg per kilo of fruit. As such its market price can fluctuate up to 28 $20,000 per kg. Metabolic engineering approaches to synthesise this molecule by 29 microbial fermentation have only resulted in low yields of up to 5 mg L -1 . In contrast, 30 cell-free synthetic biochemistry offers an intriguing compromise to the engineering 31 constraints provided by the living cell. Using purified enzymes or a two-step semi-32 synthetic route, an optimised pathway was formed for raspberry ketone synthesis 33 leading up to 100% yield conversion. The semi-synthetic route is potentially scalable 34 and cost-efficient for industrial synthesis of raspberry ketone.