Enantioselective total synthesis of the indole alkaloid 16-episilicine

Abstract

The first total synthesis of (-)-16-episilicine has been completed from a phenylglycinol-derived bicyclic lactam, the key steps being stereoselective conjugate addition and alkylation reactions, and a ring-closing metathesis.

Cyclizations of Aryl Enynes Containing Propargyl Alcohol and Diallylamine Groups to Yield Indolecarbaldehydes Induced by Ruthenium Complexes

“…In our case, a route to functionalized indoles with a carbaldehyde group is achieved. Compounds with structural motifs similar to that of 4 have been used as precursors for the synthesis of indole alkaloid 16‐episilicine24a and tricyclic carbazole derivatives,24b which show high biological anti‐inflammatory, antitumor, antibacterial, antimicrobial, and antioxidative activities.…”

Enantioselective Synthesis of Indole Alkaloids from Chiral Lactams

“…Chemoselective oxidation of the methylene carbon next to the indole 2-position of the resulting tetracycle 57 with diiodine pentoxide, followed by removal of the Boc protecting group and methylation of the resulting secondary amine, gave alkaloid (-)-16-episilicine (58). 48,49 …”

“…Chemoselective oxidation of the methylene carbon next to the indole 2-position of the resulting tetracycle 57 with diiodine pentoxide, followed by removal of the Boc protecting group and methylation of the resulting secondary amine, gave alkaloid (-)-16-episilicine (58). 48,49 As an extension of our work on the use of chiral amino alcohol derived bicyclic lactams for the enantioselective synthesis of natural products, we decided to explore the use of (S)-tryptophanol-derived bicyclic lactams for the synthesis of indole alkaloids. 50 In this case, the chiral amino alcohol would not only be a source of chirality, as in the case of phenylglycinol-derived lactams, but would also incorporate the tryptamine moiety present in many indole alkaloids.…”

Construction of Cyclohepta[b]indoles via Platinum-Catalyzed Intermolecular Formal [4+3]-Cycloaddition Reaction of α,β-Unsaturated Carbene Complex Intermediates with Siloxydienes

“…Several conventional methods such as Fischer indole synthesis, 1f-h intramolecular nucleophilic addition, 2 ring-expansion reaction, 3 ring-closing metathesis, 4 and several others 5 were utilized for the construction of this tricyclic core, and quite recently, gallium(III)-catalyzed threecomponent [4+3]-cycloaddition reaction was reported. 6 We already reported a new method for the catalytic generation of α,β-unsaturated carbene complex intermediate 2 based on the electrophilic activation of alkynes with Pt(II) catalyst, [7][8][9][10] and the generated carbene complex further reacted with vinyl ethers in a [3+2]-cycloaddition manner to give tricyclic indoles fused with a five-membered ring 3.…”