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Background: The novel bacterial topoisomerase inhibitors (NBTIs) developed in our laboratory show potent on-target enzyme inhibition but suffer from low activity against Gram-negative bacteria. Methods: With the aim of improving the antibacterial activity of our compounds against Gram-negative bacteria, we tested them in combination with different efflux pump inhibitors (EPIs), a strategy that showed promise in several other classes of antimicrobials. We also investigated the combined effect of NBTIs with ATP-competitive inhibitors of bacterial type II topoisomerases (ACIs), as well as the antibiofilm properties of our compounds and the combination with EPIs against early and mature Acietobacter baumannii biofilm. Results: Our results demonstrate that combinations of NBTIs with EPI Phenylalanine-arginyl-β-naphthylamide significantly reduce the corresponding NBTIs' minimal inhibitory concentration values and show potentiation of A. baumannii biofilm inhibition as compared to NBTIs alone. Although combinations of NBITs and ACIs did not show synergistic effects, the FIC index value calculations revealed additive effects for all the combinations of a selected NBTI in combination with three ACIs in all the assayed Gram-negative bacteria from the ESKAPE group. Conclusions: These results show for the first time that combinations of NBTIs with either EPIs or a different class of the topoisomerase inhibitors may be a beneficial strategy to combat difficult-to-treat bacterial infections. [ABSTRACT FROM AUTHOR]

Noyori–Ikariya‐type ruthenium(II)‐catalysts for asymmetric transfer hydrogenation (ATH) have been known for 25 years and have proved as a well‐behaved and user‐friendly platform for the synthesis of chiral secondary alcohols. A progress has been made in the past five years in understanding the asymmetric reduction of complex ketones, where up to four stereocenters can be controlled in a single chemical transformation. Intriguing multi‐chiral molecular architectures are therefore available in few well understood and robust synthetic steps from commercially available building blocks and possess handles for additional functionalization. The aim of this Review is to showcase the availability of three‐dimensional scaffolds and homochiral lead‐like compounds via ATH and inspire their direct use in drug discovery endeavors. Basic mechanistic insights are provided to demystify the stereo‐chemical outcomes, as well as examples of diastereoselective transformations of enantiopure alcohols to give a feeling of how these rigid non‐planar molecules can be further elaborated. [ABSTRACT FROM AUTHOR]

CF3-substituted 1,3-diols were stereoselectively prepared in excellent enantiopurity and high yield from CF3-substituted diketones by using an ansa-ruthenium(II)-catalyzed asymmetric transfer hydrogenation in formic acid/triethylamine. The intermediate mono-reduced alcohol was also obtained in very high enantiopurity by applying milder reaction conditions. In particular, CF3C(O)-substituted benzofused cyclic ketones underwent either a single or a double dynamic kinetic resolution during their reduction. [ABSTRACT FROM AUTHOR]

Stereopure CF 3 -substituted syn -1,2-diols were prepared via the reductive dynamic kinetic resolution of the corresponding racemic α-hydroxyketones in HCO 2 H/Et 3 N. (Het)aryl, benzyl, vinyl, and alkyl ketones are tolerated, delivering products with ≥95% ee and ≥87:13 syn / anti . This methodology offers rapid access to stereopure bioactive molecules. Furthermore, DFT calculations for three types of Noyori-Ikariya ruthenium catalysts were performed to show their general ability of directing stereoselectivity via the hydrogen bond acceptor SO 2 region and CH/π interactions., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The crystal structure of the title enanti-opure tetralol derivative {systematic name: (1 S ,2 S )-2-[( S )-2,2,2-tri-fluoro-1-hy-droxy-eth-yl]-1,2,3,4-tetra-hydro-naph-thalen-1-ol}, C 12 H 13 F 3 O 2 , synthesized by asymmetric transfer hydrogenation, was elucidated by low-temperature single-crystal X-ray diffraction. The enanti-opure compound crystallizes in the Sohncke space group P 2 1 2 1 2 1 with one mol-ecule in the asymmetric unit and features intra-molecular as well as inter-molecular O-H⋯O hydrogen bonding. The absolute configuration was established from anomalous dispersion effects., (© Radan et al. 2023.)

The crystal structure of the title compound, C 12 H 11 F 3 O 2 , was elucidated by low-temperature single-crystal X-ray diffraction. The enanti-opure compound crystallizes in the Sohncke space group P 2 1 and features one mol-ecule in the asymmetric unit. The structure displays inter-molecular O-H⋯O hydrogen bonding, which links the mol-ecules into infinite chains propagating parallel to [010]. The absolute configuration was established from anomalous dispersion., (© Motaln et al. 2023.)

We describe an efficient catalytic strategy for enantio- and diastereoselective synthesis of homochiral β-CF 3 , β-SCF 3 , and β-OCF 3 benzylic alcohols. The approach is based on dynamic kinetic resolution (DKR) with Noyori-Ikariya asymmetric transfer hydrogenation leading to simultaneous construction of two contiguous stereogenic centers with up to 99.9% ee, up to 99.9:0.1 dr, and up to 99% isolated yield. The origin of the stereoselectivity and racemization mechanism of DKR is rationalized by density functional theory calculations. Applicability of the previously inaccessible chiral fluorinated alcohols obtained by this method in two directions is further demonstrated: As building blocks for pharmaceuticals, illustrated by the synthesis of heat shock protein 90 inhibitor with in vitro anticancer activity, and in particular, needle-shaped crystals of representative stereopure products that exhibit either elastic or plastic flexibility, which opens the door to functional materials based on mechanically responsive chiral molecular crystals., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)