Bromonium Ion Induced Transannular Oxonium Ion Formation−Fragmentation in Model Obtusallene Systems and Structural Reassignment of Obtusallenes V−VII

Abstract

Ring-closing metathesis was used to construct the strained 11-membered ring of obtusallenes II (and IV). Bromonium-ion induced transannular oxonium ion formation-fragmentation gave the macrocyclic carbon skeleton of obtusallene VII with a bromine atom at C-13 in line with a previously published hypothesis. An additional brominated [5.5.1]bicyclotridecane adduct that must arise from a bromonium-ion induced transannular oxonium ion formation-fragmentation could also be isolated, suggesting that this adduct represents the core of an as yet undiscovered natural product. An authentic sample of obtusallene V was studied by NMR spectroscopy and the position of the halogens at C-7 and C-13 were reassigned on the basis of a 13 C NMR chlorine-induced isotopic shift. This revised structure was subsequently confirmed by X-ray crystallography. These findings allow us to confidently conclude that the structures of obtusallenes VII and VI should also be reassigned.

The Laurencia Paradox: An Endless Source of Chemodiversity

“…In the original report on the isolation of obtusallenes V (917), VI (916), and VII (910) from L. obtusa, the bromine and chlorine atoms were placed at C-7 and C-13, respectively, on the basis of analysis of the NMR spectroscopic data [770]. Several extensive investigations concerning the biosynthesis of these natural products were undertaken by Braddock and co-workers [768,789,790] that finally led to the reassignment of the position of the halogens at C-7 and C-13 on the basis of a 13 C NMR chlorine induced isotopic shift, which was further confirmed by X-ray crystallographic analysis [772]. The latter study also predicted the existence of compounds with a 4,13-dioxabicyclo[5.5.1]tridecane ring system [772].…”

“…Several extensive investigations concerning the biosynthesis of these natural products were undertaken by Braddock and co-workers [768,789,790] that finally led to the reassignment of the position of the halogens at C-7 and C-13 on the basis of a 13 C NMR chlorine induced isotopic shift, which was further confirmed by X-ray crystallographic analysis [772]. The latter study also predicted the existence of compounds with a 4,13-dioxabicyclo[5.5.1]tridecane ring system [772]. Subsequently, metabolites with this framework were isolated from Laurencia marilzae in 2011 and designated as marilzabicycloallenes A (918), B (921), C (919), and D (920) [777].…”

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

“…The latter may be altered significantly by different heteroatom substituents, as for the bromo-substituted obtusallenes V–VII 135–137 (Tables 2 and 7). Similarly, NOE data analyses (iejimalides, 138–140 scleritodermin A, 141, 142 Table 9) may be ambiguous for endocyclic double bonds if the structural constraints of the ring are not well defined.…”

Ultra‐high resolution band‐selective HSQC for nanomole‐scale identification of chlorine‐substituted 13C in natural products drug discovery

“…For example, in halohydrin 1, the Cl-and Br-substituted methine 1 H and 13 C NMR signals have almost identical δ values. [6] The structures of a surprising number of bromochloroterpenes from red algae, including violacene [8] and obtusallenes V-VII, [9] were originally misassigned, partly because of mistaken interpretation of Cl-versus Br-substituted 13 C NMR signals. Finally, contemporary methods for NMR assignments by DFT calculations, based on gauge-independent atomic orbitals (GIAO), [10] which have achieved reliable levels of accuracy in predicting 1 H and 13 C chemical shifts in many organic structures, are of little help with Br-and Cl-substituted 13 C because they poorly estimate the spin-orbit effects of heavy atoms.…”