Asymmetric Total Syntheses of the Akuammiline Alkaloids (−)‐Strictamine and (−)‐Rhazinoline

Abstract

Strictamine and rhazinoline are representative methanoquinolizidine-containing akuammiline alkaloids that possess different stereochemistry at the C16 position. Aunified approach to the enantioselective total syntheses of these two molecules is described. The key steps in this synthesis include ap hotocatalytic intra/intermolecular type II radical cascade reaction, aT suji-Trost allylation, ap alladium-or nickelmediated cyclization, and al ate-stage intramolecular Nalkylation reaction.

Engaging Diastereomeric syn‐ and anti‐6‐Bromo‐4a‐isopropyl‐2‐methyl‐2,3,4,4a‐tetrahydro‐1H‐carbazoles in Suzuki Coupling Reaction: Synthesis, Spectral Characterization and DFT Studies

“…The organic layer was dried using Na 2 SO 4 , filtered, and concentrated on Rotavapor. The crude mixture was then purified using column chromatography (eluent: a mixture of ethylacetate and n-hexane) to afford the corresponding Suzuki-coupled products (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

“…Tetrahydrocarbazole skeletons for instance, are part of many natural products providing them complex molecular structures with interesting biological potencies. Strychnos alkaloids, such as tubifoline IX, [12][13][14] and akuammilinealkaloids, strictamine (X), [15] rhazinoline (XI), [16] and scholaricine A (XII) [17] are examples of naturally occurring tetrahydrocarbazole compounds with unusual chemical structures. Arboridine (XIII), [18] isolated from Malaysian Kopsia species, is a tetrahydrocarbazole bearing alkaloid with numerous rings and unprecedented cage skeleton.…”

Applications of ultrasound in total synthesis of bioactive natural products: A promising green tool

“…In 2019, a unified approach to the enantioselective total syntheses of (–)-strictamine ( 80 ), 16- epi -strictamine ( 78 ), and (–)-rhazinoline ( 79 ) were disclosed by Qin and co-workers involving the protection of the secondary amine under ultrasonication as a key step [114] . Strictamine ( 80 ) and associated congeners such as rhazinoline ( 79 ) [115] belong to a subfamily of the akuammiline alkaloids that possess a unique methanoquinolizidine structural unit; they contain different stereochemistry at the C16 position.…”

Photochemical Rearrangements in Heterocyclic Chemistry

“…This kind of core structure is found in synthetic precursors of alkaloids such as strictamine, rhazinoline, melinonine, and strychnoxanthine. [57,58] Hoffmann′s group proposed a way of synthesizing a trifluoromethyl-substituted pyrrolo-oxazolone (Scheme 14). [59] In this study, they show the regioselectivity of photoinduced HAT.…”

“…The transformation to compound 65 , a bridged azocanone, resembles to the Norrish type II reaction. This kind of core structure is found in synthetic precursors of alkaloids such as strictamine, rhazinoline, melinonine, and strychnoxanthine , …”