Enantioselective Total Synthesis of (-)-Zygadenine.

The Veratrum alkaloids are highly complex steroidal alkaloids characterized by their intricate structural and stereochemical features and exhibit a diverse range of pharmacological activities. A new synthetic pathway has been developed to access this family of natural products, which enabled the first total synthesis of (-)-zygadenine. This synthetic route entails the construction of a hexacyclic carbon skeleton through a stereoselective intramolecular Diels-Alder reaction, followed by a radical cyclization. Subsequently, a meticulously designed sequence of redox manipulations was optimized to achieve the de novo synthesis of this highly oxidized Veratrum alkaloid.

Total Synthesis of (+)-Isolysergol.

The enantioselective synthesis of (+)-isolysergol was completed in 18 steps, and an overall yield of 11% was obtained from (2R)-(+)-phenyloxirane as a chiral pool. Key features of the synthesis include a stereoselective intramolecular 1,3-dipolar addition of nitrone with terminal olefin and a Cope elimination to furnish the D ring. A rhodium-catalyzed intramolecular [3 + 2] annulation of a benzene ring with α-imino carbenoid was designed to afford the 3,4-fused indole scaffold at the late stage of the synthesis.

Dealkenylative Ni-Catalyzed Cross-Coupling Enabled by Tetrazine and Photoexcitation.

A new and general method to functionalize the C(sp3)-C(sp2) bond of alkyl and alkene linkages has been developed, leading to the dealkenylative generation of carbon-centered radicals that can be intercepted to undergo Ni-catalyzed C(sp3)-C(sp2) cross-coupling. This one-pot protocol leverages the easily procured alkene feedstocks for organic synthesis with excellent functional group compatibility without the need for a photoredox catalyst.

Total Synthesis of (-)-Batrachotoxinin A: A Local-Desymmetrization Approach.

An enantioselective total synthesis of (-)-batrachotoxinin A is accomplished based on a key photoredox coupling reaction and the subsequent local-desymmetrization operation. After the expedient assembly of the highly oxidized steroid skeleton, a delicate sequence of redox manipulations was carried out to deliver a late-stage intermediate on gram scale-and ultimately (-)-batrachotoxinin A in an efficient manner.

Total Synthesis of (-)-Chanoclavine I and an Oxygen-Substituted Ergoline Derivative.

An efficient and direct route to ergot alkaloid (-)-chanoclavine I (3) is described using the inexpensive compound (2R)-(+)-phenyloxirane (15) as a chiral pool in 13 steps with 17% overall yield. Key features of the synthesis include a palladium-catalyzed intramolecular aminoalkynylation of terminal olefin and a rhodium-catalyzed intramolecular [3 + 2] annulation. An oxygen-substituted ergoline derivative (-)-25 was also achieved by using the same strategy.

Formal synthesis of (±)-cycloclavine.

An efficient formal synthesis of (±)-cycloclavine is achieved in seven steps and 27% overall yield from the known 2-(4-bromo-1-tosyl-1H-indol-3-yl)acetaldehyde. Key features include an iron(III)-catalyzed aza-Cope-Mannich cyclization and an intramolecular Heck reaction or a self-terminating 6-exo-trig aryl radical-alkene cyclization.