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Temperature-dependent ' Hand I3C-NMR spectra reveal that polyhalogenated marine B-chamigrenes or synthetic derivatives thereof which are trans-diequatorially substituted at C(8) and C(9), such as rogiolol ((-)-2), obtusol ((+)-3), and their acetates (+)-I and (-)-4, undergo slow ring-A chair-chair inversion. Conformational equilibria and kinetics are investigated with the aid of synthetic model compounds and molecular-mechanics calculations. Thus, steric repulsions between Br,,-C(2) and H,,-C(7) are seen to disfavor thermodynamically conformers Ib, 2b, 3b, and 4h, which can only he detected through cross-saturation transfer, while additional steric repulsions between Me,,-C(1) and OH,,-C(3) make conformer 8h of ohtusol epimer so scarcely populated that it can not be detected. In agreement, with (+)-9 and (+)-lo, which have a trigonal C(2), two conformers can he directly observed by NMR. The kinetic barriers, which are seen to arise mainly from steric repulsions between H,,-C( ) and the axial H or halogen atoms at C(8) and C(lO), are calculated and discussed with respect to well documented exocyclicmethylidene-substituted cyclohexane(ene) systems. This helps to rationalize why in rogiolol acetate ((+)-1) ring B is unusually inert towards Zn/Et20/AcOH which causes bromohydrine-group elimination from ring A.
1. Introduction.
-We have recently reported that the /I-chamigrene derivative rogiolol acetate ((+)-1) is peculiar under at least three respects [l]. First, (+)-1 was isolated from a marine sponge (Spongia zimocca) [l], which was a phylum unknown to contain chamigranes; possibly (+)-1 is biosynthesized in this sponge from a precursor obtained from a nearby growing red seaweed of the genus Luurencia [l] (now identified as Luurencia microcludiu KUTZNING [2]), which would constitute an unprecedented example of food chain2). Second, ring B of (+)-1 proved inert toward the reducing reagent Zn/Et,O/ AcOH, which was found to induce elimination of the bromohydrine group from ring A instead; this contrasts with the behavior of both obtusol ((+)-3) and isoobtusol ((+)-5) I)