Conformational Studies of Marine Polyhalogenated α‐Chamigrenes Using Temperature‐dependent NMR spectra inverted‐chair and twist‐boat cyclohexane moieties in the presence of an axial halogen atom at C(8)

Abstract

a-Chamigren-3-one (+)-8 bearing an axial C1-atom at C(8) exists as a largely dominant conformer with MeeC(5) at the envelope-shaped enone ring pointing away from CI,,-C(8) at the cyclohexane ring ( = B) in the 'normal' chair conformation, as shown by 'H-NMR. In contrast, the a -chamigren-3-ols (+)-9 and (+)-lo, obtained from hydride reduction of (+)-8, show a temperature-dependent equilibrium of conformers where the major conformers have ring B in the inverted-chair (and twist-boat for (+)-9) conformation to avoid repulsions between Me-C(5) and CI,,-C(8) (Scheme 1). This is in agreement with the conformation of the epoxidation product (+)-12 of (+)-9 where Me-C(5) is pushed away from CI,,-C(8) in a ring-B chair similar to that of (+)-8 (Scheme 2). Introduction of a pseudoequatorial Br-atom at C(2) of (+)-8, as in enone (+)-15 (Scheme 3 ) , does not affect the conformation; but a pseudoaxial Br-C(2) experiences repulsive interactions with H,,-C(7), as shown by the 'H-NMR data of the isomeric enone (+)-16 where the 'normal'-chair conformer Ca-16 is in an equilibrium with the inverted chair conformer ICP-16 (Scheme 3 ) . These results and the accompanying paper allow a unifying view on the conformational behavior of marine polybalogenated a -chamigrenes. This view is supported by the acid-induced isomerization of c( -chamigrene (+)-9 (inverted chair) to 8-chamigrene (+)-17 ('normal' chair; Scheme 4 ) , the driving force being the lesser space requirement of CH2=C(5) than of Me-C(5). This explains why P-chamigrenes are so common in nature.

The Laurencia Paradox: An Endless Source of Chemodiversity

“…Moreover, less frequently halogenation on a double bond or a conjugated bromodiene system is incorporated into the second six-membered ring. In the 1990s, Guella and co-workers undertook thorough conformational studies of α-and β-chamigrenes using temperaturedependent NMR spectra [164,472,473]. Majusculone (130) and mailione (131) are the only two known nor-chamigranes isolated from a number of different Laurencia species [118,122,128,134,142,143,147].…”

Progress in the Chemistry of Organic Natural Products 102

“…Aplysistatin L. filiformis [341], L. flexilis [331], L. implicata [91,114], L. karlae [333], L. luzonensis [334], L. saitoi [335], L. similis [325], L. snackeyi [118,150,[328][329][330]339] Palisadin A L. flexilis [331], L. implicata [91,114], L. karlae [333], L. luzonensis [323,334], L. saitoi [335], L. similis [325], L. snackeyi [118,150,328 -L. mariannensis [198] (continued) seco-chamigrane (470)(471)(472)(473)(474) not designated (486) not designated (488)(489) not designated (484) pacifigorgiane (485) guaiane (480) poitane (precapnellane) (478)(479) oppositane (481)(482)(483) seco-laurokamurane (469) germacrane (466) humulane (467)…”