The plakortones, novel bicyclic lactones from the sponge Plakortis halichondrioides: Activators of cardiac SR-Ca2+-pumping ATPase

Plakortethers A−G: A New Class of Cytotoxic Plakortin−Derived Metabolites

“…As well as a plethora of cycloperoxides closely resembling the parent compound and antibiotic plakortin (1), [2] Plakortis sponges have also furnished some structurally related metabolites in the forms of furano esters and plakortones, [3] which lack the peroxide function but still possess the same parent cycloperoxide carbon framework. In the furano esters, such as compound 2, [4] a single oxygen atom connects C(3) and C (6); in the plakortones [such as plakortone E (3)] [5] a γ-lactone bond connecting C(1) and C(4) is also present.…”

“…[3] The richness and the variety of pharmacologically active secondary metabolites found in these sponges have prompted us to intensify our chemical investigations into the Caribbean specimen Plakortis simplex. As we have already reported, this organism produces plakortin (in remarkable amounts), [4] other known (e.g., plakortide H) and novel (e.g., dihydroplakortin and plakortide J) [1,4] cyclic peroxides, and related bioactive compounds belonging to the classes of furanoesters and of plakortones.…”

Use of furans in synthesis of bioactive compounds

“…Our own research programs in the quest of natural and non-natural molecules lately have centered around the use of furan or substituted furans as precursor [3]. In this connection, we have recently completed the total synthesis of several naturally occurring compounds such as prehispanolone (1) [4], syringolides 1 (2a) and 2 (2b) [5], and echinofuran (3) [6].In this article, we wish to discuss our synthetic approaches to the total synthesis of plakortone B (4) [7], which was isolated and identified via a bioassay-guided fractionation of the ethyl acetate extract of Jamaican marine sponge Plakortis halichondrioides [8]. It was reported that 4 belongs to a novel class of activators of cardiac sarcoplasmic reticulum -Ca 2+ -pumping ATP synthase at µM concentration [8].…”

“…In this article, we wish to discuss our synthetic approaches to the total synthesis of plakortone B (4) [7], which was isolated and identified via a bioassay-guided fractionation of the ethyl acetate extract of Jamaican marine sponge Plakortis halichondrioides [8]. It was reported that 4 belongs to a novel class of activators of cardiac sarcoplasmic reticulum -Ca 2+ -pumping ATP synthase at µM concentration [8].…”

“…It was reported that 4 belongs to a novel class of activators of cardiac sarcoplasmic reticulum -Ca 2+ -pumping ATP synthase at µM concentration [8]. Our synthetic attempts commenced from 3-bromofuran (5) [9] and the chiral aldehyde (6) [10] as precursors.…”