Protecting-group-free synthesis of (+)-ent-kauradienone and (À)-jungermannenone C has been accomplished through sequential applications of three radical-based reactions, including late-stage photoinduced skeletal rearrangements of bicyclo[3.2.1]octene ring systems. Further investigations on various terpenoids showed good functional-group tolerance and suggest that some terpenoids could also be produced via such photoinduced rearrangements pathways in nature. Our work demonstrates how paying more attention to unconventional radical mechanisms can reveal new chemistries that facilitate the synthesis of complex natural products.

Background 211At is a high-energy α-ray emitter with a relatively short half-life and a high cytotoxicity for cancer cells. Its dispersion can be imaged using clinical scanners, and it can be produced in cyclotrons without the use of nuclear fuel material. This study investigated the biodistribution and the antitumor effect of 211At-labeled gold nanoparticles (211At-AuNP) administered intratumorally. Results AuNP with a diameter of 5, 13, 30, or 120 nm that had been modified with poly (ethylene glycol) methyl ether (mPEG) thiol and labeled with 211At (211At-AuNP-S-mPEG) were incubated with tumor cells, or intratumorally administered to C6 glioma or PANC-1 pancreatic cancers subcutaneously transplanted into rodent models. Systemic and intratumoral distributions of the particles in the rodents were then evaluated using scintigraphy and autoradiography, and the changes in tumor volumes were followed for about 40 days. 211At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration, 211At-AuNP-S-mPEG became localized in the tumor and did not spread to systemic organs during a time period equivalent to 6 half-lives of 211At. Tumor growth was strongly suppressed for both C6 and PANC-1 by 211At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with 211At-AuNP-S-mPEG with a diameter of 5 nm. Conclusions The intratumoral single administration of a simple nanoparticle, 211At-AuNP-S-mPEG, was shown to suppress the growth of tumor tissue strongly in a particle size-dependent manner without radiation exposure to other organs caused by systemic spread of the radionuclide. Graphic Abstract

Ac oncise and enantioselective total synthesis of (+ +)-jungermatrobrunin A( 1), whichf eatures au nique bicyclo[3.2.1]octene ring skeleton with an unprecedented peroxideb ridge,w as accomplished in 13 steps by making use of al ate-stage visible-light-mediated Schenck ene reaction of (À)-1a,6a-diacetoxyjungermannenone C( 2). Along the way, aU V-light-induced bicyclo[3.2.1]octene ring rearrangement afforded (+ +)-12-hydroxy-1a,6a-diacetoxy-ent-kaura-9(11),16dien-15-one (4). These divergent photo-induced skeletal rearrangements support apossible biogenetic relationship between (+ +)-1,(À)-2,and (+ +)-4.