A biologically attractive and structurally unique marine natural product, (+)-liphagal, was biomimetically synthesized in 29 % overall yield in a longest linear sequence of 13 steps from commercially available (+)-sclareolide. This synthesis involved the following crucial steps: (i) stereocontrolled hydrogenation of an endo-olefinic decalin to install the C8 stereogenic centre present in the requisite decalin segment;[a]
A biologically attractive and structurally unique marine natural product, (+)‐strongylin A (1), was synthesized for the first time by starting from a known trans‐decalone derivative (19 % overall yield in 11 steps). The synthetic method involved the following key steps: (i) stereocontrolled hydrogenation of an exo‐olefinic decalin to install the C8 stereogenic centre present in the required decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; and (iii) sequential BF3·Et2O‐induced dehydroxylation/rearrangement/cyclization of a decalin tertiary alcohol to directly produce target compound 1. This total synthesis has established the absolute configuration of the natural product.
Effective control of drug release from “nano-prodrugs”, which are nanoparticles composed of water-insoluble prodrug compounds is one of the most important determinants of the balance between drug efficacy and side effects. However, the chemical behaviors of nano-prodrugs in relation to drug release are poorly characterized. We created nano-prodrugs using a series of fatty acid ester (C2–C18) derivatives of 7-ethyl-10-hydroxycamptothecin (SN-38) and found that their in vitro cytotoxic activities decreased as the length of the fatty acid chain increased. The cytotoxicities of these nano-prodrugs were unrelated to particle size or efficacy of cellular uptake, but critically depended on their hydrolysis rate within cancer cells. These results indicated that the drug release rate from nano-prodrugs can be controlled successfully by changing the length of the introduced fatty acid chain.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.