Total Synthesis of (+)‐Strongylin A, a Rearranged Sesquiterpenoid Hydroquinone from a Marine Sponge

Abstract

A biologically attractive and structurally unique marine natural product, (+)‐strongylin A (1), was synthesized for the first time by starting from a known trans‐decalone derivative (19 % overall yield in 11 steps). The synthetic method involved the following key steps: (i) stereocontrolled hydrogenation of an exo‐olefinic decalin to install the C8 stereogenic centre present in the required decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; and (iii) sequential BF3·Et2O‐induced dehydroxylation/rearrangement/cyclization of a decalin tertiary alcohol to directly produce target compound 1. This total synthesis has established the absolute configuration of the natural product.

A Concise Route for the Synthesis of Tetracyclic Meroterpenoids: (±)-Aureol Preparation and Mechanistic Interpretation

“…Physical and spectroscopic properties of synthetic (±)-aureol ((±)-1) matched those previously reported for the natural compound [2]. Thus, the synthesis of (±)-aureol ((±)-1) from (±)-albicanol (5) was completed in only seven steps and a global 28% yield, substantially improving the synthetic procedures previously published [11][12][13][14][15][16][17][18][19][20]. Moreover, a simple epimerization of aureol (1) to 5-epi-aureol (11) has The synthesis of (±)-aureol ((±)-1) (Scheme 2) used as starting material (±)-albicanol (5), which was prepared through Cp 2 TiCl-catalyzed radical cascade cyclization of epoxy-farnesyl acetate, as previously reported by us and others [24,25].…”

“…Although the tetracyclic meroterpenoids have exclusive structural features and a wide assortment of biological activities, only one highly modular and robust platform for the synthesis of this class of natural products has been reported to date [ 10 ]. The rest of the reported routes are synthetic operations (10–27 linear steps) that have not enabled straightforward access to the whole family of these interesting natural products [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Bioactive Prenyl- and Terpenyl-Quinones/Hydroquinones of Marine Origin †

“…In this type of natural product, it is common to determine the molecular constitution and the relative stereochemistry, but the absolute configuration sometimes remains unassigned until the total synthesis is performed, either starting from an enantiomerically pure natural compound, or using stereocontrolled reactions. This is the case for (+)-strongylin A ( 137 ) [ 69 ], (+)-aureol ( 131 ) [ 70 ], and (−)-cyclosmenospongine ( 138 ) [ 71 ], which have been recently reported ( Figure 19 ).…”

Unified Synthesis of the Marine Sesquiterpene Quinones (+)‐Smenoqualone, (–)‐Ilimaquinone, (+)‐Smenospongine, and (+)‐Isospongiaquinone

“…Intermediate 5 , in turn, would be formed by the coupling reaction of an appropriately functionalized trans ‐decalin 6 with triply oxy‐substituted aryllithium compound 8 (accessible from known trioxygenated benzene derivative 7 ). Starting material 6 is readily prepared from an enantiomerically pure (+)‐5‐methyl Wieland–Miescher ketone ( 9 ) in an eight‐step sequence according to the method previously reported by us …”