Synthesis of Three Marine Natural Sesterterpenolides from Methyl Isoanticopalate. First Enantioselective Synthesis of Luffolide

Abstract

[Reaction: see text]. The synthesis of three marine sponge metabolites, luffolide (4), 5, and 6, are described for the first time, establishing the absolute configuration of these compounds. The key intermediate, aldehyde 17, was obtained from methyl isoanticopalate, 11. The addition of 3-furyllithium to 17 and subsequent photochemical oxidation give the gamma-hydroxybutenolide 5 and its epimer at C-16. Sesterterpenolide 6 is obtained by dehydration of 5. From the key aldehyde 17, luffolide (4) was obtained in six steps.

Marine natural products

“…478 Enantiospecific syntheses of luffolide, isolated from a Luffariella species, 479 16,25-dihydroxycheilantha-13( 24),17-dien-19,25-olide and 25-hydroxycheilantha-13 (24),15,17-trien-19,25-olide, isolated from an Ircinia species, 480 have been reported. 481 A series of cytotoxic, highly degraded steroids, demethylincisterols A 1 -A 4 477-480 were isolated from a Homaxinella species (Korea). In the same study, four butoxyderivatised sterols, homaxisterols A 1 -A 4 481-484, were also isolated from the same sponge.…”

Diterpenoids

“…There have been reports of the synthesis of the marine norsesquiterpene (+)austrodoral from sclareol, 19 (−)-Thioambrox R from sclareolide, 20 6b-isovaleryloxylabda-8,13-diene-7a,15-diol from larixol, 21 (−)marginatone from (+)-coronarin E, 22 and the sesterterpenoid luffolide from methyl isocopalate. 23 Some Michael adducts to unsaturated ketones derived from readily available hispanolone have shown 24 useful activity against the rice blast fungus, Magnoporthe grisea (Pyricularia oryzae). The electro-oxidation of hispanolone has been examined; 25 some of the products have anti-inflammatory activity.…”

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.02,6]decane skeleton

“…As an alternative, the epoxidation of rac - 13 with MCPBA was investigated, which delivered the spirocyclic exo -configured epoxide rac - 16 in 46% overall yield from rac - 9 as the sole diastereomer. Lewis acid-catalyzed rearrangement of rac - 16 with BF 3 etherate [32] furnished the desired aldehyde rac - 15 in 26% yield (12% overall yield from rac - 9 ) and the tetracyclic N , O -acetal rac - 17 in 35% yield. The latter compound is presumably formed from rac - 15 by a Lewis acid-catalyzed, intramolecular, and thus proximity-facilitated tandem hydride transfer/cyclization sequence [33].…”