Asymmetric Total Synthesis of Norzoanthamine.

We report herein the asymmetric total synthesis of norzoanthamine using radical reactions as key steps for rapid access to the congested carbocyclic core, which is the major synthetic challenge for most zoanthamine alkaloids. (1) The Ueno-Stork radical cyclization was applied to construct the adjacent quaternary centers at the C-9 and C-22 positions; (2) a Co-catalyzed HAT radical reaction was successfully applied to construct the quaternary center at C-12 via Csp3 -Csp2 bond formation; (3) a Mn-catalyzed HAT radical reaction was used to stereospecifically reduce the tetra-substituted olefin (C13=C18) and install the contiguous stereocenters in proximity to the quaternary center. A one-pot bio-inspired cyclization step was finally applied to forge the unstable bis-amino acetal skeleton. Our approach can precisely control the stereochemistry of seven vicinal stereocenters and effectively construct the highly congested heptacyclic skeleton.

Synthesis of ent-Cleistanthane Diterpenoid Spruceanol: Construction of an Aromatic C Ring via Lewis Acid-Controlled Regioselective Diels-Alder Cycloaddition.

The first synthesis of ent-cleistanthane-type diterpenoid spruceanol with significant anticancer activity is described. A chiral pool approach was employed with a linear sequence of 13 steps beginning from readily available and inexpensive andrographolide. The approach features the construction of an aromatic ring with hydroxyl and methyl groups at C-12 and C-13 of the target compound, respectively, via Lewis acid-controlled regioselective Diels-Alder cycloaddition and the regioselective removal of the primary hydroxyl group of the Diels-Alder adduct.

Total Synthesis of Viridin and Viridiol.

The asymmetric total synthesis of (-)-viridin and (-)-viridiol, antifungal metabolites, was achieved in 17 and 18 steps from a commercially available starting material. An intramolecular [3+2] cycloaddition was applied to an easily available l-ribose derivative in order to construct the highly substituted D ring containing the key chiral cis-triol fragment. Co-catalyzed metal-hydride H atom transfer (MHAT) radical cyclization was utilized to form the C-ring and the all-carbon quaternary center at C-10. This convergent strategy provides a scalable approach to prepare viridin and viridiol for biological studies.

Double-Modal Locomotion of a Hydrogel Ultra-Soft Magnetic Miniature Robot with Switchable Forms.

Flexible miniature robots are expected to enter difficult-to-reach areas in vivo to carry out targeted operations, attracting widespread attention. However, it is challenging for the existing soft miniature robots to substantially alter their stable shape once the structure is designed. This limitation leads to a fixed motion mode, which subsequently restricts their operating environment. In this study, we designed a biocompatible flexible miniature robot with a variable stable form that is capable of adapting to complex terrain environments through multiple movement modes. Inspired by the reversible stretching reaction of alginate saline gel stimulated by changes in environmental ion concentration, we manufactured a morphologically changeable super-soft hydrogel miniature robot body. According to the stretch and contraction shapes of the flexible hydrogel miniature robot, we designed magnetic fields for swing and rolling motion modes to realize multi-shape movement. The experimental results demonstrate that the deflection angle of the designed flexible miniature robot is reversible and can reach a maximum of 180°. The flexible miniature robot can complete forward swinging in the bar stretch state and tumbling motion in the spherical state. We anticipate that flexible hydrogel miniature robots with multiple morphologies and multimodal motion have great potential for biomedical applications in complex, unstructured, and enclosed living environments.

Synthesis and anticancer activity of some novel indolo[3,2-b]andrographolide derivatives as apoptosis-inducing agents.

A series of novel indolo[3,2-b]andrographolide derivatives were designed, synthesized and screened in vitro against three human cancer cell lines MCF7 (human breast cancer), HCT116 (human colon cancer), and DU145 (human prostate cancer). Fourteen compounds 6b, 6e, 6i, 6j, 6l, 6m, 6n, 12a, 12b, 13a, 13b, 15a, 17a, and 17b exhibited better anti-cancer activities than andrographolide for all three human cancer lines, with compound 6l displaying best activity with IC50 values of 1.85, 1.22 and 1.24 µM against MCF7, HCT116 and DU145 respectively. Preliminary anti-cancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 6l against HCT116 using flow cytometry, and the results suggested that compound 6l inhibited tumor proliferation through inducing early and late cellular apoptosis in a concentration-dependent manner and causing cell cycle arrest in the S-phase.