Leucascandrolide B, a new 16-membered, extensively methyl-branched polyoxygenated macrolide from the calcareons sponge Leucascandra caveolata from northeastern waters of New Caledonia

We report a novel, extensively methyl-branched and polyoxygenated 16-member ed macrolide, leucascandrolide B (= (1R*,5S*,7R*,9S*,13R*:,14R*,15R*,11Z)-5 -[(E)-1,4-dimethylhept-5-enyl]-1,7,9-trihydroxy-11,14-dimethyl-3-oxo-4,17-d ioxabicyclo[11.3.1]heptadec-11-en-15-yl] carbamate; 2), isolated from the c alcareous sponge Leucascandra caveolata BOROJEVIC and KLAUTAU from the nort heastern coast of New Caledonia. The NMR structural assignments were corrob orated by semisynthetic derivatives of 2, the functional groups and atom co nnectivity by derivatives 4-6 (obtained by acetylation, oxidation, and elim ination-solvation, reap.), and the relative configurations by derivative 7 (obtained by carbonation). The preferred conformation of 2, centered on a c hair-like tetrahydro-2H-pyran ring formed by intramolecular acetalization, was derived from molecular mechanics and semiempirical calculations which w ere in agreement with all NMR data. A dilactone `dimeric' structure 3, indi stinguishable from 2 on the basis of all above data, was ruled out by tande m MS-MS experiments.