Synthesis of alkaloids by Stevens rearrangement of nitrile-stabilized ammonium ylides: (±)-laudanosine, (±)-laudanidine, (±)-armepavine, (±)-7-methoxycryptopleurine, and (±)-xylopinine.

The Stevens rearrangement of nitrile-stabilized ammonium ylides in conjunction with the reductive removal of the nitrile function permits the facile construction of α-branched amines from α-aminonitriles. We employed this reaction sequence for the preparation of (±)-laudanosine, (±)-laudanidine and (±)-armepavine, (±)-7-methoxycryptopleurine, and (±)-xylopinine from two closely related and readily accessible bicyclic α-aminonitriles. The final products were obtained in high to almost quantitative yields (71–98%) from the quaternary ammonium salts obtained by N-alkylation of these starting materials.

Xylochemie – Naturstoffsynthese aus Holz

Titelbild: Xylochemie – Naturstoffsynthese aus Holz (Angew. Chem. 47/2015)

Cover Picture: Xylochemistry-Making Natural Products Entirely from Wood (Angew. Chem. Int. Ed. 47/2015)

Xylochemistry--Making Natural Products Entirely from Wood.

The first total synthesis of the dimeric berberine alkaloid ilicifoline (ilicifoline B) is reported. Its carbon skeleton is constructed from ferulic acid, veratrole, and methanol. The synthesis reported herein employs starting materials solely derived from wood. The natural product is thus constructed entirely from renewable resources. The same strategy is applied to a formal total synthesis of morphinan alkaloids. The use of wood-derived building blocks (xylochemicals) instead of the conventional petrochemicals represents a sustainable alternative to classical synthetic approaches.

A five-step synthesis of (±)-tylophorine via a nitrile-stabilized ammonium ylide.

The Stevens rearrangement of a nitrile-stabilized ammonium ylide is the key step of a very short and practical synthesis of the phenanthroindolizine alkaloid (±)-tylophorine. The method requires only five linear steps and is devoid of any protecting group manipulations.

CCDC 1412268: Experimental Crystal Structure Determination

Related Article: Daniel Stubba, Günther Lahm, Mario Geffe, Jason W. Runyon, Anthony J. Arduengo III, Till Opatz|2015|Angew.Chem.,Int.Ed.|54|14187|doi:10.1002/anie.201508500