Second-Generation Atroposelective Synthesis of KRAS G12C Covalent Inhibitor GDC-6036.

A chromatography-free asymmetric synthesis of GDC-6036 (1) was achieved via a highly atroposelective Negishi coupling of aminopyridine 5 and quinazoline 6b catalyzed by 0.5 mol % [Pd(cin)Cl]2 and 1 mol % (R,R)-Chiraphite to afford the key intermediate (Ra)-3. An alkoxylation of (Ra)-3 with (S)-N-methylprolinol (4) and a global deprotection generates the penultimate heterobiaryl intermediate 2. A controlled acrylamide installation by stepwise acylation/sulfone elimination and final adipate salt formation and crystallization delivered high-purity GDC-6036 (1).

Three-dimensional printing of mycelium hydrogels into living complex materials.

Biological living materials, such as animal bones and plant stems, are able to self-heal, regenerate, adapt and make decisions under environmental pressures. Despite recent successful efforts to imbue synthetic materials with some of these remarkable functionalities, many emerging properties of complex adaptive systems found in biology remain unexplored in engineered living materials. Here, we describe a three-dimensional printing approach that harnesses the emerging properties of fungal mycelia to create living complex materials that self-repair, regenerate and adapt to the environment while fulfilling an engineering function. Hydrogels loaded with the fungus Ganoderma lucidum are three-dimensionally printed into lattice architectures to enable mycelial growth in a balanced exploration and exploitation pattern that simultaneously promotes colonization of the gel and bridging of air gaps. To illustrate the potential of such mycelium-based living complex materials, we three-dimensionally print a robotic skin that is mechanically robust, self-cleaning and able to autonomously regenerate after damage.

Living materials made by 3D printing cellulose-producing bacteria in granular gels.

Bacterial cellulose is an attractive resource for the manufacturing of sustainable materials, but it is usually challenging to shape it into elaborate three-dimensional structures. Here, we report a manufacturing platform for the creation of complex-shaped cellulose objects by printing inks loaded with bacteria into a silicone-based granular gel. The gel provides the viscoelastic behavior necessary to shape the bacteria-laden ink in three dimensions and the gas permeability required to sustain cellular growth and cellulose formation after the printing process. Using Gluconacetobacter xylinus as model cellulose-producing bacteria, we study the growth and the mechanical properties of cellulose fiber networks obtained upon incubation of the printed inks. Diffusion processes within the ink were found to control the growth of the cellulose structures, which display mechanical properties within the range expected for conventional hydrogels. By keeping the bacteria alive in the printed object, we produce living materials in complex geometries that are able to self-regenerate their cellulose fiber network after damage. Such living hydrogels represent an enticing development towards functional materials with autonomous self-healing and self-regenerating capabilities.

Fabrication and Design of Wood-Based High-Performance Composites.

Delignified densified wood is a new promising and sustainable material that possesses the potential to replace synthetic materials, such as glass fiber reinforced composites, due to its excellent mechanical properties. Delignified wood, however, is rather fragile in a wet state, which makes handling and shaping challenging. Here we present two fabrication processes, closed-mold densification and vacuum densification, to produce high-performance cellulose composites based on delignified wood, including an assessment of their advantages and limitations. Further, we suggest strategies for how the composites can be re-used or decomposed at the end-of-life cycle. Closed-mold densification has the advantage that no elaborate lab equipment is needed. Simple screw clamps or a press can be used for densification. We recommend this method for small parts with simple geometries and large radii of curvature. Vacuum densification in an open-mold process is suitable for larger objects and complex geometries, including small radii of curvature. Compared to the closed-mold process, the open-mold vacuum approach only needs the manufacture of a single mold cavity.