Forwards and backwards – synthesis of Laurencia natural products using a biomimetic and retrobiomimetic strategy incorporating structural reassignment of laurefurenynes C–F

Abstract

The synthesis and structural reassignment of laurefurenynes C–F has been achieved, with the new structures fitting with a proposed biosynthesis. Also reported is the synthesis of ent-laurencin and ent-deacetyllaurencin via a retrobiomimetic approach.

Marine natural products

“…410 The biomimetic total synthesis of laurefurenynes C-F 921-924 has necessitated their structural revision as shown. 411 Reviews of relevance to the Rhodophyta include a summary of bioactive red algal oxylipins, 412 a summation of the impact of seaweeds (primarily Rhodophyta) on enteric methane production in ruminants, 413 and an assessment of the nutraceutical value of red algae and their metabolites. 414 D-Isooriside is a common algal metabolite that has been shown to have protective effects against alcohol-induced hepatoxicity.…”

“…410 The biomimetic total synthesis of laurefurenynes C–F 921–924 has necessitated their structural revision as shown. 411…”

Total Synthesis and Structure Confirmation of (E) and (Z)-Ocellenyne

“…natural product family that could arise biosynthetically by opening of the oxonium ions 4 and 7 with various nucleophiles. We have characterized the four oxonium ions 4 and 7 and studied their opening with a variety of nucleophiles, as well as completing the synthesis of numerous C 15 Laurencia natural products. ,,, …”

“…Inspired by the Scheuer et al bromination of an ocellenyne derivative, we reasoned that selective bromination of diene 15 would yield both desired diastereomers of the syn -vicinal-dibromide (see 16 and 17 ) en route to ent-(E/Z)- 5 and ( E/Z ) - 8 , with the syn -stereochemistry being set by the cis -olefin geometry of 15 (Scheme ). This diene 15 could ultimately be obtained from diacetone- d -glucose, which utilizes chemistry previously developed by our group. , We started from known epoxide 9 , and added lithiated 1-butyne to the terminal epoxide position using the method by Yamaguchi and Hirao to yield homopropargylic alcohol 10 (Scheme ). In the presence of P-2 nickel boride catalyst, hydrogen, and ethylenediamine, the alkyne underwent stereospecific reduction to give the corresponding ( Z )-homoallylic alcohol, which upon acetylation, gave the acetate 11 .…”

“…Exposure of 14 to sodium hydride promoted intramolecular S N 2 cyclization, which gave the key 6,10- anti -2,5-dioxabicyclo­[2.2.1]­heptane 15 in 90% yield. Initial bromination studies with 15 showed good selectivity for the internal olefin; however, significant degradation was observed, potentially from reaction of the pendant cyclic ether with the intermediate bromonium ion. ,, This problem was ameliorated by addition of excess lithium bromide, which delivered the pair of syn -12,13-dibromide diastereomers 16 and 17 (d.r. = 1.1:1), which were separated by supercritical fluid chromatography (SFC) .…”