Chemical structures, biosynthesis, bioactivities, biocatalysis and semisynthesis of tobacco cembranoids: An overview

Cembranoids, 14-membered carbocyclic diterpenes composed of four isoprene units, are mainly found in plants of the Nicotiana and Pinus genera, as well as in soft coral and other marine organisms. We summarise the chemical structures of the eighty-seven naturally occurring tobacco cembranoids (1-52), nor-cembranoids (53-74), seco-cembranoids (75-82) and cyclised cembranoids (83-87) reported to date. The most prevalent cembranoids in tobacco are (1S,2E,4S,7E,11E)-cembra-2,7,11-triene-4,6-diol (1) and (1S,2E,412,7E,11E)-cembra-2,7,11-triene-4,6-diol (2), which are biosynthesised in the plastid from the reactions of geranylgeranyl diphosphate with cembrantrien-ol synthase and cytochrome P450 hydroxylase via the 2-C-methyl-D-erythritol-4-phosphate metabolic pathway. The accumulation of cembranoids in tobacco is affected by genetic and environmental factors, including fertiliser, water and light exposure, soil-type and temperature. Tobacco-derived cembranoids are known to display antifungal, antibacterial, anti-human immunodeficiency virus, anti-tumour and neuroprotective properties. A large number of biologically active (primarily anti-invasive, anti-prolifeiative, anti-migratory and neuroprotective) compounds have been prepared from the semisynthesis of tobacco cembranoids, many via biocatalytic methods. The documented bioactivities of tobacco cembranoids make them excellent templates for the future development of drugs to treat cancer, AIDS, Alzheimer's disease, Parkinson's disease, stroke and other neurodegenerative diseases. These findings indicated that although tobacco has long been associated with negative effects on human health, it may ultimately be able to play a therapeutic role. (c) 2015 Elsevier B.V. All rights reserved.