Enantioselective Synthesis of (−)‐Halenaquinone

Abstract

The efficient, 12-14 step (LLS) total synthesis of (À)-halenaquinone has been achieved. Keys teps in the synthetic sequence include:(a) proline sulfonamide-catalyzed, Yamada-Otani reaction to establish the C6 all-carbon quaternary stereocenter,( b) multiple,n ovel palladium-mediated oxidative cyclizations to introduce the furan moiety,a nd (c) oxidative Bergman cyclization to form the final quinone ring.

Use of chiral auxiliaries in the asymmetric synthesis of biologically active compounds: A review

“…Using the above protocol, Goswami et al synthesized (−)‐halenaquinone, an unnatural member of the class of steroidal furans. Its natural enantiomer, (+)‐ halenaquinone, was isolated by Scheuer and Clardy in 1983 from the marine sponge Xestospongia exigua and was shown to have antibiotic activity against the bacteria Staphylococcus aureus and Bacillus subtilis .…”

“…In sequence, 30 was subjected to thermal elimination under microwave radiation, followed by cyclohexenone ring formation using lithium bis (trimethylsilyl)amide (LiHMDS) and benzotriazole formaldehyde surrogate 31 to obtain the alcohol 32 . Compound 32 was the key intermediate for the construction of the furan ring, from which (−)‐halenaquinone was obtained after some chemical manipulations …”

Ring Forming Approaches to para-Quinones: Toward a General Diels–Alder Disconnection

“…To the best of our knowledge, only one example of an oxidative Bergman cyclization in natural product synthesis has been reported. 28 In 2018, Carter and co-workers disclosed a 14-step synthesis of (–)-halenaquinone, forging the 1,4-naphthoquinone moiety using the reaction conditions first reported by Grissom. 26 Thus, diyne 21 was heated at 160 °C in the presence of excess TEMPO.…”

Concise Synthesis of (±)‐Myrioneurinol Enabled by Sequential [2+2] Cycloaddition/Retro‐Mannich Fragmentation/Mannich Reaction

“…With tricycle 17 j in hand, we sought next to assemble the 1,3‐oxazine ring. Methylenation of 17 j under the conditions of NaOMe and paraformaldehyde proceeded uneventfully to give rise to dienone 23 in 82 % yield [10] . After exhaustive attempts, the requisite 1,3‐oxazine moiety was built up to deliver the tetracyclic core 25 of myrioneurinol, presumably by way of 24 , in a cascade fashion featuring Boc cleavage, N‐hydroxymethylation and an intramolecular oxy‐Michael addition in the presence of TFA and formalin [2a,b, 3c] .…”