Briarellins J−P and Polyanthellin A:  New Eunicellin-Based Diterpenes from the Gorgonian Coral Briareum polyanthes and Their Antimalarial Activity

Abstract

A new chemical study of the hexane extract of the gorgonian Briareum polyanthes collected in Puerto Rico afforded 10 new diterpenes of the eunicellin class, briarellins 1-9 and polyanthellin A (10), along with the known diterpene briarellin D (11). The structures and relative stereochemistry of metabolites 1-10 were assigned on the basis of NMR studies, chemical methods, and comparisons to the spectral properties of 11. A reassessment of prior structural assignment for briarellin A and two known sclerophytin-type diterpenes, 13 and 14, is proposed. Antimalarial tests on 1-6 and 8-12 indicated that they were active against Plasmodium falciparum.The considerable structural diversity of the terpene metabolites produced by Caribbean gorgonian octocorals is widely recognized by both natural products and synthetic chemists alike. Specifically, specimens from this region belonging to the genus Briareum (syn: Solenopodium, order Gorgonacea, phylum Cnidaria, family Briareidae) have been the subject of several chemical investigations which thus far have led to the isolation of two related classes of 2,11-cyclized cembranoids. 1 Of these, the asbestinins are the most abundant, whereas the eunicellins (briarellins) constitute a significantly smaller group. 2,3 Briarellin-type diterpenoids have also been isolated from the Taiwanese soft coral Pachyclavularia violacea. 4 The unique and complex architecture of these two groups of natural products has made them irresistible targets for total synthesis. 5 Recently, we have focused our attention on the gorgonian Briareum polyanthes (Duchassaing & Michelotti) collected on the southwest coast of Puerto Rico. Two previous investigations of this gorgonian from Bermudian and Puerto Rican waters had led largely to complex mixtures of chlorinated and nonchlorinated 3,8-cyclized cembranoids known as briareins (briantheins and briareolides). 6,7 From this soft coral, we now wish to report the isolation and structural elucidation of 10 new eunicellintype diterpenes (also known as cladiellins and sclerophytins), briarellins J-P (1-9) and polyanthellin A (10). The known compound briarellin D (11), previously isolated by us from the gorgonian octocoral Briareum asbestinum, was also isolated in the course of this investigation. 3a This is the first time that diterpenes based on this type of carbon skeleton are reported in B. polyanthes. Results and DiscussionHealthy and robust specimens of B. polyanthes were collected by hand using scuba at -10 m in Cabo Rojo, Puerto Rico. The animal specimens were frozen, freezedried, cut in small pieces, and homogenized exhaustively using a mixture of CHCl 3 -MeOH (1:1) to obtain, after in vacuo concentration, an extract that was fractionated using our standard partitioning procedure into several fractions of differing polarity. 8 The hexane fraction was purified by size-exclusion chromatography on a Bio-Beads SX-2 column with toluene followed by repeated chromatography on Si gel flash columns to give pure compounds 1-11. Briarellin D (11), a minor compone...

Peroxy natural products

“…One eunicellin-type diterpenoid astrogorgin G 169 has been repored from a Chinese gorgonian Astrogorgia sp., 89 92 and this study has also led to a revision of the structure of previously reported briarellin A 93 to 174. The structure originally assigned to 11-acetoxy-4-deacetoxyasbestinin F 94 has been revised to 175.…”

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

“…Misassignments of single stereocenters (Table 7) near to correctly assigned centers are associated with interpretation of NOE data for structurally diverse compounds. For example, this is the case for brevenal, 61, 62 solandelactones A-H, 63, 64 ritterazines B 65, 66 and F, 67 netamines E and G, 68, 69 briarellin J, 70, 71 and dictyosphaeric acid A. 72, 73 Consideration of the source of these errors highlights the need for careful evaluation of all possible alternative molecular models that adhere to NOE constraints.…”

Asymmetric Total Synthesis and X‐Ray Crystal Structure of the Cytotoxic Marine Diterpene (+)‐Vigulariol

“…[2] (+)-1 has shown to exhibit cyctotoxity against A 549 (human lung adenocarcinoma) cell culture at an IC 50 of 18.33 mg mL À1 . [1] Two other soft-coral diterpenes sclerophytin A (2) [3,4] and polyanthellin A (3) [5,6] have shown high cytotoxicity and antimalarial activity, respectively. Their attractive molecular architectures and their diverse biological activities previously led to several ingenious total syntheses of some members of this natural product family by the research groups of Paquette, [3a,c] Overman, [3b,c, 7] Crimmins, [8] and Kim.…”