High levels of halogenated natural products in large pelagic fish from the Western Indian Ocean

Concentrations, profiles and muscle-liver distribution of halogenated natural products (HNPs) and anthropogenic persistent organic pollutants (POPs) were investigated in five large pelagic fish species and one smaller planktivore fish species from the Western Indian Ocean. Analysis of swordfish muscle from the Seychelles revealed the predominance of HNPs, with the highest concentrations found for 2′-methoxy-2,3′,4,5′- tetraBDE (2′-MeO-BDE 68 or BC-2), 6-methoxy-2,2′,4,4′- tetraBDE (6-MeO-BDE 47 or BC-3) and 2,3,3′,4,4′,5,5′-heptachloro-1′-methyl-1,2′-bipyrrole (Q1), along with varied contributions of further HNPs. The mean concentration of ∑HNPs (330 ng/g lw) was one or two orders of magnitude higher than ∑DDTs (60 ng/g lw) and ∑PCBs (6.8 ng/g lw). HNPs (BC-2, BC-3 and Q1) were also predominant in individual samples of three tropical tuna species from the Seychelles and from other regions of the Western Indian Ocean (Mozambique Channel, off Somalia and Chagos Archipelago). Non-targeted gas chromatography coupled with electron capture negative ion mass spectrometry operated in the selected ion monitoring mode (GC/ECNI-MS-SIM) analysis of one swordfish sample indicated low abundance of rarely reported HNPs (three hexachloro-1′-methyl-1,2′-bipyrrole (Cl6-MBP) isomers and pentabromo-1,1′-dimethyl-2,2′-bipyrroles (Br5-DBP)) but no further abundant unscreened polyhalogenated compounds.

Capturing Nature's Oxonium Ions

<p><a></a>Acetylcholine and <i>S</i>-adenosylmethionine exemplify the tetraalkylammonium (R₄N⁺) and trialkylsulfonium (R₃S⁺) ions used by Nature. The corresponding trialkyloxonium ions (R₃O⁺), however, do not play a central role in biology most likely due to their hydrolytic instability compared with their ammonium and sulfonium counterparts. Indeed, Meerwein’s salts [(CH₃)₃O⁺BF₄^– and (CH₃CH₂)₃O⁺BF₄^–], the simplest of the trialkyloxonium ions, are among the most powerful alkylating agents known, and they too are unstable to water. Only recently have water stable trialkyloxonium ions been reported which contain an oxatriquinane skeleton. Interestingly, despite the inherent hydrolytic instability of the vast majority of trialkyloxonium ions, they have been postulated as key intermediates in the biosynthesis of a number of complex natural products from <i>Laurencia</i> species. The existence of these complex trialkyloxonium ions has been implied from the structural and stereochemical diversity of these natural products and is supported by elegant biomimetic total syntheses, yet no direct evidence for their existence has been forthcoming. Herein, we report the synthesis and full characterisation of one family of these biosynthetically relevant trialkyloxonium ions - the most structurally and stereochemically complex oxonium ions characterised to date. Additionally, the elucidation of their <i>in vitro </i>reactivity profile has resulted in the synthesis of more than ten complex halogenated natural products. This work substantiates the existence of complex trialkyloxonium ions as key reactive intermediates in the biosynthesis of numerous halogenated natural products from <i>L. </i>spp. – expanding Nature’s rich inventory of onium ions.</p>

Capturing Nature's Oxonium Ions

<p><a></a>Acetylcholine and <i>S</i>-adenosylmethionine exemplify the tetraalkylammonium (R₄N⁺) and trialkylsulfonium (R₃S⁺) ions used by Nature. The corresponding trialkyloxonium ions (R₃O⁺), however, do not play a central role in biology most likely due to their hydrolytic instability compared with their ammonium and sulfonium counterparts. Indeed, Meerwein’s salts [(CH₃)₃O⁺BF₄^– and (CH₃CH₂)₃O⁺BF₄^–], the simplest of the trialkyloxonium ions, are among the most powerful alkylating agents known, and they too are unstable to water. Only recently have water stable trialkyloxonium ions been reported which contain an oxatriquinane skeleton. Interestingly, despite the inherent hydrolytic instability of the vast majority of trialkyloxonium ions, they have been postulated as key intermediates in the biosynthesis of a number of complex natural products from <i>Laurencia</i> species. The existence of these complex trialkyloxonium ions has been implied from the structural and stereochemical diversity of these natural products and is supported by elegant biomimetic total syntheses, yet no direct evidence for their existence has been forthcoming. Herein, we report the synthesis and full characterisation of one family of these biosynthetically relevant trialkyloxonium ions - the most structurally and stereochemically complex oxonium ions characterised to date. Additionally, the elucidation of their <i>in vitro </i>reactivity profile has resulted in the synthesis of more than ten complex halogenated natural products. This work substantiates the existence of complex trialkyloxonium ions as key reactive intermediates in the biosynthesis of numerous halogenated natural products from <i>L. </i>spp. – expanding Nature’s rich inventory of onium ions.</p>

Halonium-Induced Polyene Cyclizations

This review covers the methods that chemists have developed to access halogenated polycyclic structures from polyenes, by emulating Nature’s enzymatic machineries. From pioneering studies to the most recent developments, the different strategies, whether based on the use of standard reagents or on the design of specific ones, will be presented. Finally, asymmetric reactions and applications for the total synthesis of natural products will be exposed.1 Introduction2 Pioneering Studies3 Use of Specific Reagents4 Use of N-Haloamides5 Asymmetric Reactions6 Total Synthesis of Halogenated Natural Products7 Conclusion and Perspectives

Capturing Nature's Oxonium Ions

<p><a></a>Acetylcholine and <i>S</i>-adenosylmethionine exemplify the tetraalkylammonium (R₄N⁺) and trialkylsulfonium (R₃S⁺) ions used by Nature. The corresponding trialkyloxonium ions (R₃O⁺), however, do not play a central role in biology most likely due to their hydrolytic instability compared with their ammonium and sulfonium counterparts. Indeed, Meerwein’s salts [(CH₃)₃O⁺BF₄^– and (CH₃CH₂)₃O⁺BF₄^–], the simplest of the trialkyloxonium ions, are among the most powerful alkylating agents known, and they too are unstable to water. Only recently have water stable trialkyloxonium ions been reported which contain an oxatriquinane skeleton. Interestingly, despite the inherent hydrolytic instability of the vast majority of trialkyloxonium ions, they have been postulated as key intermediates in the biosynthesis of a number of complex natural products from <i>Laurencia</i> species. The existence of these complex trialkyloxonium ions has been implied from the structural and stereochemical diversity of these natural products and is supported by elegant biomimetic total syntheses, yet no direct evidence for their existence has been forthcoming. Herein, we report the synthesis and full characterisation of one family of these biosynthetically relevant trialkyloxonium ions - the most structurally and stereochemically complex oxonium ions characterised to date. Additionally, the elucidation of their <i>in vitro </i>reactivity profile has resulted in the synthesis of more than ten complex halogenated natural products. This work substantiates the existence of complex trialkyloxonium ions as key reactive intermediates in the biosynthesis of numerous halogenated natural products from <i>L. </i>spp. – expanding Nature’s rich inventory of onium ions.</p>