In 2002, Sinninghe Damste et al. showed that two anaerobic ammonium-oxidizing (anammox) bacteria contained a series of unusual lipids that had up to five linearly fused cyclobutane moieties with cis ring junctions (please also see the News & Views piece by Edward DeLong). These bacteria convert nitrite and ammonia into nitrogen gas in an organelle-like structure called the anammoxosome.
These unusual lipids had staircase-like structures, so the authors named these compounds “ladderanes.” They proposed that the presence of these fatty acids turned the anammoxosome membrane into “a tight barrier against diffusion,” which they postulated was necessary to “maintain concentration gradients during the exceptionally slow anammox metabolism and to protect the remainder of the cell from the toxic anammox intermediates” (for example, hydrazine and hydroxylamine).
The enantioselective synthesis of one of these unusual fatty acids – pentacycloanammoxic acid – was recently reported in the March 15th issue of the Journal of the American Chemical Society (Enantioselective Synthesis of Pentacycloanammoxic Acid by Mascitti & Corey). Several years ago, these same authors reported the racemic synthesis of this compound (Total Synthesis of (+/-)-Pentacycloanammoxic Acid), but this is the first enantioselective synthesis of this ladderane and it may be possible to use this enantiomerically pure compound to determine how these “ladderanes” are made in vivo. Mascitti & Corey discussed this briefly in the paper: “[i]f the biosynthesis were to occur by a cascade-type polycyclization, it would have to be novel in terms of the chemistry used because of the unfavorable energetics and the paucity of the known chemical reactions of this type.” They also said “unraveling the biosynthetic mechanism … [will be] as challenging as the chemical synthesis” – I don’t know about you, but I can hardly wait to read the paper that explores the mechanism of ladderane synthase…
Joshua Finkelstein (Associate Editor, Nature)