Mar DrugssfsMar Drugssfs.doc

Mar Drugs. 2015 Apr; 13(4): 2407–2423. Published online 2015 Apr 20.?doi:??10.3390/mPMCID:?PMC4413218 Synthesis and Bioactivity of Luffarin I Aitor Urosa,1?Isidro S. Marcos,1?David Díez,1?Anna Lithgow,2?Gabriela B. Plata,3?José M. Padrón,3?and?Pilar Basabe1,* Valeria Costantino,?Academic Editor Author information???Article notes???Copyright and License information?? Go to: Abstract The first synthesis of Luffarin I, sesterterpenolide isolated from sponge?Luffariella geometrica, has been accomplished from commercially available sclareol. The key strategy involved in this synthesis is the diastereoselective reduction of an intermediate ketone. Luffarin I against human solid tumor cell lines showed antiproliferative activities (GI50) in the range 12–17 μM. Keywords:?luffarin I, sclareol, diastereoselective reduction, sponges, sesterterpenolide, marine metabolites Go to: 1. Introduction During the last few years, there has been intensive research for new natural pharmacologically active compounds. In general, the chemistry of marine organisms and of sponges in particular has led to the discovery of a great number of novel and interesting metabolites [1]. Many marine-living organisms have developed toxic secondary metabolites to defend themselves against predators [2]. There is a group of pentaprenyl terpenoids whose structures are derivable from geranylfarnesyl diphosphate, known as sestertepenoids, of frequent occurrence in marine sponges. The diverse bioactivity of sesterterpenoids has made them attractive targets for both biomedical and synthetic purposes [3]. Marine sponges have been the source of a large number of relevant sesterterpenes with biological activities, including anti-feedant [4,5,6], platelet-aggregation inhibition [7,8] and anti-inflammatory [9,10]. The luffarins (A–N),?1–14,?Figure 1, were isolated by Butler and Capon from an Australian marine sponge,Luffariella geometrica?[11]. Luffarins are sesterterpenolides that have in common with the