Total Synthesis of (−)-Stemonine

Abstract

[reaction: see text] An enantioselective total synthesis of (-)-stemonine (1) is reported via a convergent assembly of the acyclic precursor 2. Key transformations include a Staudinger-aza-Wittig reaction to form the central perhydroazepine ring system and an iodine-induced tandem cyclization to construct the pyrrolidino-butyrolactone framework.

Total Synthesis of Azumamides A and E

“…[6] The homoallylic acetate [7] 11 was obtained through a highly diastereo-and enantioselective (d.r. > 99 %; 98 % ee [8] ) crotylation performed with the chiral reagent (+)-(E)-crotyl-Ipc 2 -borane on the readily available 3-benzyloxypropanal (10). The subsequent reductive ozonolysis [9] furnished variable ratios of the regioisomeric acetates 12 and 13.…”

“…The subsequent reductive ozonolysis [9] furnished variable ratios of the regioisomeric acetates 12 and 13. K 2 CO 3 -mediated hydrolysis of the mixture of acetates and regioselective silylation of the diol 14 produced the requested (2R,3S)-1-[(tert-butyldiphenylsilyl)oxy]-5-benzyloxy-2-methyl-3-pentanol (15 We thus performed a highly stereoselective Wittig olefination [10] by reacting the diprotected aldehyde 19 with the ylide formed from the phosphonium salt 20.…”

Total Syntheses of Bisdehydroneostemoninine and Bisdehydrostemoninine by Catalytic Carbonylative Spirolactonization

“…[1] These alkaloids are categorized into eight different groups and most of them feature ac haracteristic pyrrolo[1,2-a]azepine nucleus.O ur recent interest in oxaspirolactone synthesis [2] and the stemofoline group [3] brought our attention to the stemoamide group because many of its members,such as bisdehydroneostemoninine (1a,F igure 1A), (iso)bisdehydrostemoninine (1b and 1c), [4] stemoninines Aa nd B( 1d and 1e), [5] tuberstemoamide (1f), [6] sessilifoliamide A(1g), [7] (dihydro)stemoninine (1hand 1i), [8] and stemoenonine (1j), [9] contain an oxaspirolactone moiety.Despite the recent efforts toward the total syntheses of stemona alkaloids, [10] only afew members of the stemoamide group have been synthesized. While there are over 20 total syntheses of the simplest member stemoamide (1l, Figure 1B), [11] total syntheses of the more complex ones are very rare.N otably,W illiams and coworkers reported the first total synthesis of stemonine (1m)in 2003 [12] and Chida, Sato and co-workers developed au nified approach to synthesize both 1mand saxorumamide (1n)from 1l in 2017. [13] So far, there have been no reported total syntheses of these oxaspirolactone-containing stemona alkaloids (1a-k).…”

“…We later found out that the use of freshly prepared Waymouth catalyst provided 9a from 8 as asingle isomer in 54 %yield. It was speculated that the freshly prepared Waymouth catalyst may be able to promote an in situ epimerization process.With 9a in hand, the Eschenmoser protocol was used to install an a-exo-methylene group and provide the compound 17.R u 3 -(CO) 12 -catalyzed isomerization of the exo-methylene to an endocyclic double bond completed the first total synthesis of bisdehydroneostemoninine (1a)inits racemic form. [23] Notably, 1a was produced in an overall 68 %y ield from 9a with only one column purification.…”

A Versatile Enantioselective Synthesis of Azabicyclic Ring Systems: A Concise Total Synthesis of (+)‐Grandisine D and Unnatural Analogues

“…stemona alkaloid, stemonine (5), [3] and the manzamine alkaloid, nakadomarin A (6), [4] to highlight but a few representative examples. Other related natural products contain the corresponding lactam moiety, such as 7-9.…”