Nature chemistry最新文献

The Strychnos alkaloids have long been regarded as landmark targets for chemical synthesis due to their captivating architectures and notorious biological properties. However, the design of approaches that access multiple family members in an asymmetric, concise and atom-economical fashion remains an important challenge. Here we show that thiophene S,S-dioxides (TDOs) offer a modular, rapid entry to Strychnos natural products via inverse electron demand Diels-Alder cascades. We demonstrate that exceptional levels of stereocontrol can be achieved in asymmetric TDO cycloadditions, affording tricyclic indolines of utility in medicinal chemistry research and enabling the stereoselective synthesis of eight Strychnos alkaloids by the shortest routes described so far, including a synthesis of the iconic family member brucine. Using a machine-learning approach, computational studies provide insight into the source of stereoinduction and reveal an intriguing and unexpected spontaneous cheletropic extrusion of SO₂.

Life's development and adaption to fluctuating environments are underpinned by DNA-protein interactions, which have also spurred the development of artificial systems ranging from genetic circuits to nanoarchitectures. Nonetheless, in cellulo there remains an untapped design space for DNA-protein systems that are incompatible with the role of DNA as genetic material. Here we engineer retrons to intracellularly express non-genetic small DNAs embedding specific protein-binding sequences. These DNA species are products of genes and therefore their quantitative, spatial and functional control is decoupled from genetic stability, enabling alternative architectures of DNA-protein systems with unique functions. Using synthetic networks of proteins and the engineered retron-DNA, we demonstrated precise, multiplexed gene regulation and construction of feedback circuits for dynamic responses. Further, we developed DNA-based molecular scaffolds and bridges that enable modular, post-translational and spatial control of multiple proteins within cells. Finally, we transformed an allosteric transcription factor into inducible post-translational switches. Our work suggests that the non-genetic DNA-protein systems represent a promising control layer for creating synthetic cellular behaviours.

The structural anisotropy necessary to distinguish clockwise from counterclockwise motions in motor-molecules continuously rotating about a covalent single bond has previously been supplied by chiral fuelling systems or by enzymes. Here we report a class of rotary motors in which, like motor proteins, structural asymmetry in the motor itself causes directional rotary catalysis. A single stereogenic centre in azaindole-phenylethanoic acid motors is sufficient to produce diastereomeric intermediates of atropisomeric conformations in the catalytic cycle, generating 8:1 clockwise:counterclockwise directional bias in the motor's rotary catalysis of diisopropylcarbodiimide hydration (motor substituent PhCH₂-). One enantiomer of a chiral hydrolysis promoter increases the directionality to 30:1 for clockwise rotation (motor substituent CH₃-), while the other enantiomer reverses the direction to 1:2 clockwise:counterclockwise. The experimental demonstration that a chiral molecular motor can be powered by a chemical fuel to rotate either with, or counter to, the motor's dominant power stroke informs the understanding of how chemical energy is transduced through catalysis, the fundamental process that powers biology.