An Efficient Total Synthesis of (±)-Lycoramine

Abstract

[reaction: see text] A short and unique approach to (+/-)-lycoramine as one of the galanthamine-type alkaloids has been efficiently developed. The alternative advantage lies in that three stereocenters, including a crucial quaternary carbon center, were constructed with high diasteroselectivity via a key one-step NBS-mediated semipinacol rearrangement of the allylic alcohol.

Gram Scale Synthesis of the C(18)−C(34) Fragment of Amphidinolide C

“…The combined organic layers were washed with brine, dried (MgSO4), filtered through a thin pad of silica on top of a thin pad of celite and concentrated under reduced pressure to yield 8 as a yellow oil (145 mg, 0.61 mmol, 67%) which was used without further purification. Rf 0.23 (70% EtOAc/Hex); 1 ((2R,3R,5R)-5-((tertbutyldimethylsilyloxy)methyl)-3-methyltetrahydrofuran-2-yl)methanol (9). To a solution of alcohol (8) (1.56 mg, 6.6 mmol, 1 eq) in CH2Cl2 (100 mL) was added imidazole (830 mg, 12.3 mmol, 2 eq), followed by TBSCl (994 mg, 6.6 mmol, 1 eq) and DMAP (5 mg, catalytic).…”

Electrophilic C12 Building Blocks for Alkaloids: 1,1 Iterative Organoiron‐Mediated Routes to (±)‐Lycoramine and (±)‐Maritidine

“…There has been considerable attention paid to the development of synthetic routes to lycoramine [27] and galanthamine, [28] and since Martin and Garrison's short route [29] to lycoramine from o-vanilin, there have been significant advances [30,31,32] but only quite recently has the first enantioselective synthesis been reported. [33] Typically, the methods now preferred for the direct construction of the quaternary centre use palladium catalysed [31,34] or radical [35,36] cyclisations to alkenes, but an unusual photochemical intramolecular cyclisation of an activated arene to cyclohexenone has also provided a highly original basis for a total synthesis.…”

“…[37] The Martin and Garrison approach [29] (using anions developed from enamines), and a later Robinson annellation approach, [38] however, are among the few [39] completed syntheses that use nucleophile addition to electrophilic centres to build this hindered quaternary centre at a late stage in the route. Indeed, some of the most recent and successful developments have employed rearrangement reactions (semipinacol [30] and Cope [31] rearrangements) to side-step this problem and gradually build up the steric challenge of these targets.…”

Synthesis of the tetracyclic skeleton of the galanthamine-type Amaryllidaceae alkaloids

“…A number of total syntheses for galanthamine 2,3 and lycoramine [3][4][5][6][7] have been developed. These methods employ various approaches to building up the C-8a quaternary spiro carbon atom and the A-D rings.…”