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

Abstract

The marine sesquiterpene quinones (+)‐smenoqualone, (–)‐ilimaquinone, (+)‐smenospongine, and (+)‐isospongiaquinone were efficiently synthesized in a unified manner starting from a known trans‐decalin derivative, which is accessible from (+)‐5‐methyl Wieland–Miescher ketone. The synthetic method involved the following key steps: (i) assembly of the whole carbon skeleton by coupling the decalin segment to an aromatic moiety; (ii) p‐quinone formation by strategic salcomine oxidation of phenolic intermediates; (iii) direct conversion of (–)‐ilimaquinone into (+)‐isospongiaquinone by pTsOH‐induced isomerization of the C‐4 olefinic double bond; (iv) site‐selective amination of a dimethoxy‐p‐quinone intermediate by substitution of the C‐18 methoxy group with an amino group; and (v) one‐step construction of the requisite tetracyclic core structure by sequential BF3·Et2O‐induced rearrangement/cyclization of an olefinic decalin intermediate having an aromatic moiety. The syntheses of (+)‐smenoqualone and (+)‐smenospongine are reported here for the first time.

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].…”

Marine natural products

“…502 A large number of indole-containing alkaloids have been synthesised including makaluvamine O and batzelline D, 503 dictyodendrin G, 504 leucettamine C, 505 isonaamidine E, 506 and cylindradine B, 507 while both enantiomers of the bromotyrosine itampolin A have been produced. 508 Smenospongine A, 509 smenoqualone, 509,510 dehydrocyclospongiaquinone-1, 511 haterumadienone (done in a protecting group-free manner), 512 cheloviolenes A, B and dendrillolide C, 513 astakolactin (revised to 1217), 514 phorbaketal A, 515,516 alotaketals B, C and D, 516 and ansellones A, B and phorbadione 517 are all terpenoids that had syntheses published in 2017. One notable synthetic campaign was published by Kishi's group.…”

A Ring‐Distortion Strategy from Marine Natural Product Ilimaquinone Leads to Quorum Sensing Modulators

“…Cyclosmenospongine ( 11 ), 31 and 32 were formed stepwise by means of a Wagner–Meerwein shift/olefin addition with a 30 % global yield. Notably, by using Faulkner's conditions, postulated intermediate 30 was isolated[13a], alongside ortho ‐quinone 33 . Compound 33 was then converted into two steps into smenaqualone ( 34 ).…”