Total Syntheses of Bisdehydroneostemoninine and Bisdehydrostemoninine by Catalytic Carbonylative Spirolactonization

Abstract

The first total syntheses of the stemona alkaloids bisdehydroneostemoninine and bisdehydrostemoninine in racemic forms have been achieved. The synthetic strategy features a novel palladium-catalyzed carbonylative spirolactonization of a hydroxycyclopropanol to rapidly construct the oxaspirolactone moiety. It also features a Lewis acid promoted tandem Friedel-Crafts cyclization and lactonization to form the 5-7-5 tricyclic core of the target stemona alkaloids.

Asymmetric Total Synthesis of Sarpagine and Koumine Alkaloids

“…[15] Additionally,r ing-opening addition of cyclopropanol to iminium ions or imines is underexplored, although cyclopropanol is widely used as an ucleophilic C3 synthon. [11] Appropriate oxidants and catalysts are key to the success for the tetrahydro-b-carbolines.Chiral cyclopropanol 5a was prepared in three steps from l-tryptophan (Scheme 2A)and then evaluated under the original conditions for the tetrahydroisoquinolines( CuCl 2 /air). [13] Although the desired bridged product 6a was indeed observed in the messy reaction mixture,h owever,t he isolated yield was low (< 20 %) and inconsistent.…”

“…We envisioned that atandem amine oxidation and cyclopropanol ring-opening cyclization of substrate 5a would allow rapid assemble of the azabicyclo[3.3.1]nonane skeleton and introduction of av ersatile ketone group. [10] Enantiopure 5a with adictating chiral carbon center can be directly synthesized via Kulinkovich cyclopropanation of ac arboxyl ester, [11] which can be easily derived from the cheap chiral starting material l-tryptophan. [12] Results and Discussion Bicyclo[3.3.1]…”

Pd-catalyzed reactions of cyclopropanols, cyclobutanols and cyclobutenols

“…56). 53 A simplified catalytic cycle is proposed in Scheme 17. The C-C cleavage of the cyclopropyl ring of 17 A affords 17 B which is in equilibrium with hemiketal 17 C. Subsequent insertion of carbon monoxide into the C-Pd bond gives 17 D, from which the oxaspirolactone is formed by intramolecular trapping by the hydroxyl, possibly through the formation of palladacycle 17 E. 54 Several key intermediates have been identified from high-resolution electrospray ionization mass spectrometry monitoring of the reaction.…”

Total Synthesis of Racemic (±)-Parvistemonine A

“…到目前为止, parvistemonine A 还没有半合成或全合成报道. 在前期研究工作中, 应用路易斯酸催化的傅克反应 及内酯化的串联反应, 构建了百部生物碱的核心 [5-7-5] 反式并环结构, 并经过过渡金属催化的插羰和环化串联 反 应 , 完 成 了 天 然 产 物 bisdehydroneostemoninine 和 bisdehydrostemoninine 的合成 [12] . 我们设想能否通过关…”