Briarane Diterpenes from Micronesian Gorgonians

Four new briaranes, nui-inoalides A-D, (6-9) are described.They were isolated from octocorals collected in Pohnpei and Ant atoll, Micronesia.The absolute stereochemistry of the known briarane juncin E (5) was determined.Nuiinoalide A (6) and the known gemmacolides A, B, and D (2-4) exhibit immunomodulatory activity.Briaranes (1) are diterpenoid y-lactones of a highly substituted bicyclo[8.4.0] system.From the isolation of briarane A by Ciereszko and coworkers in 19773 up to recent papers by Kobayashi et a1.4 and by He andFaulkners more than 50 representatives of this class of compounds have been isolated from gorgonians, sea pens, and occasionally their predators.Faullcner's papers dealing with constituents of Junceella gemmacea from Pohnpei, Micronesia, appeared after our work dealing with the same gorgonian from the same location had been completed.We isolated seven briaranes, four known (2-5) and three new (6-8) compounds; a fourth new briarane (9) was isolated from an octocoral collected at Ant atoll, Micronesia, in 1987.The freeze-dried Pohnpei animal (0.42 kg dry) was extracted with ethyl acetate.The residue was chromatographed on a silica flash column, from which the hriaranes eluted with ethyl acetate.Final separation was achieved by hplc on a C18 reversed phase column with aqueous methanol gradient elution, in the order 4,7,6,8,3,2,5, in yields ranging from 1x104 to 3x10-3% (wet wt).Briarane (9) was isolated by normal phase hplc (ethyl acetate/methylene chloride) and crystallized from methanol.Spectral data (lH and 13C nmr, ir, uv, ms, [ a ] ~) of briaranes (2-4) were identical with those reported by He and Faullcne6 for gemmacolide A (2). B (3). and D (4).while the data for briarane (5) matched those reported by Kashman and coworkers6 from a Red Sea gorgonian (Junceella juncea) constituent juncin E.