Iridium-Catalyzed Enantioselective Indole Cyclization: Application to the Total Synthesis and Absolute Stereochemical Assignment of (-)-Aspidophylline A.

The first enantioselective total synthesis of (-)-aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. This strategy relies on the direct use of 2,3-disubstituted indoles with secondary allylic alcohols appended at C2 and heteronucleophiles appended at C3, indoles which are easily prepared from simple starting materials under C-H activation conditions.

Enantioselective Total Synthesis of (-)-Alstoscholarisine A.

We report a concise and highly enantioselective total synthesis of (-)-alstoscholarisine A (1), a recently isolated monoterpenoid indole alkaloid that has significant bioactivity in promoting adult neuronal stem cells proliferation. A highly enantioselective (99% ee), intramolecular Ir-catalyzed Friedel-Crafts alkylation of indole 9 with a secondary allylic alcohol was utilized to establish the first stereogenic center upon which the other three contiguous chiral centers were readily set by a highly stereoselective tandem 1,4-addition and aldol reaction. The key tetrahydropyran was constructed through a hemiacetal reduction, and the final aminal bridge was forged by a one-pot reductive amination/cyclization.

Collective total synthesis of tetracyclic diquinane Lycopodium alkaloids (+)-paniculatine, (-)-magellanine, (+)-magellaninone and analogues thereof.

The collective total synthesis of tetracyclic diquinane Lycopodium alkaloids, (+)-paniculatine, (-)-magellanine, (+)-magellaninone, and two analogues (-)-13-epi-paniculatine and (+)-3-hydroxyl-13-dehydro-paniculatine, has been accomplished. By logic-guided addition of a strategically useful hydroxyl group at C-3 of paniculatine, the formidable tetracyclic core was rapidly synthesized utilizing a site-specific and stereoselective aldol cyclization, thus making the ABD → ABCD tetracyclic approach to diquinane Lycopodium alkaloids attainable for the first time.

Isolation and complete structural assignment of Lycopodium alkaloid cernupalhine A: theoretical prediction and total synthesis validation.

Cernupalhine A (1) is a trace Lycopodium alkaloid (0.7 mg) possessing a new C17N skeleton with an unusual hydroxydihydrofuranone motif newly isolated from Palhinhaea cernua L. Its complete structural assignment, including absolute stereochemistry, was established through a combination of high-field NMR techniques and computational methods and further unequivocal confirmation by the first asymmetric total synthesis.