Short Synthesis of the Monoterpene Indole Alkaloid (±)-Arbornamine

Abstract

The first total synthesis of the monoterpene indole alkaloid (±)-arbornamine (1) has been completed, which proceeds in only 6 steps and 31% overall yield from three readily available, known compounds. The synthesis features a cascade involving a Pictet-Spengler cyclization/intramolecular ammonolysis to create the tetracyclic core of arbornamine (1) in a single chemical operation. The subsequent elaboration of 5 into 1 was effected by a key reductive Heck reaction and global reduction.

Reductive Cross-Coupling of Vinyl Electrophiles

“…This catalytic system was applied by Cook and co-workers for the synthesis of (-)-geissoschizol 66 and Yang and co-workers for the concise synthesis of (±)-arbornamine (Scheme 24). 67…”

Reductive Heck Reaction: An Emerging Alternative in Natural Product Synthesis

“…Cascade reactions were used to generate the tetracyclic core of arbornamine 110 (Scheme ) . Ni‐catalyzed reductive Heck reaction has been employed in a key step to access arbornamine skeleton.…”

Copper(I)‐Catalyzed N‐Carboxamidation of Indoles with Isocyanates: Facile and General Method for the Synthesis of Indole‐1‐carboxamides

“…Indole derivatives have become attractively synthetic goal in organic chemistry, because the indole skeleton is an important element of both natural products and synthetic molecules that exhibit a wide range of bioactivities, such as monoterpene indole alkaloids, indole alkaloids and tryptophan‐derived substances, and their application as tubulin polymerization inhibitors was also studied The development of efficient methods for their generation has attracted increasingly attentions . Transition metal‐catalyzed (such as Pd‐, Cu‐ or Rh‐ catalysts) intramolecular cyclization of functionalized o ‐alkynylanilines is one of the most efficient approaches for the synthesis of indoles.…”