Stereoselective Total Syntheses of Three Lycopodium Alkaloids, (−)-Magellanine, (+)-Magellaninone, and (+)-Paniculatine, Based on Two Pauson−Khand Reactions

Abstract

The total syntheses of (-)-magellanine, (+)-magellaninone, and (+)-paniculatine were completed from diethyl l-tartrate via the common intermediate in a stereoselective manner. The crucial steps in these syntheses involved two intramolecular Pauson-Khand reactions of enynes: the first Pauson-Khand reaction constructed the bicyclo[4.3.0] carbon framework, the corresponding A and B rings of these alkaloids in a highly stereoselective manner, whereas the second Pauson-Khand reaction stereoselectively produced the bicyclo[3.3.0]skeleton, which could be converted into the C and D rings of the target natural products.

Development of an Enantioselective Route toward the Lycopodium Alkaloids: Total Synthesis of Lycopodine

“…The Evans laboratory recently reported an elegant total synthesis of a similar alkaloid ring system (clavolonine) 10. Additionally, numerous other total syntheses of structural different lycopodium alkaloids have been reported over the past decade by Bosch,11 Chang,12 Comins,13 Dake,14 Johnston,15 Liao,16 Mukai,17 Overman,18 Sarpong,19 Siegel,20 Toste,21 Takahashi22 and Takayama 23. Herein, we disclose a full account of our work towards the alkaloid lycopodine.…”

Synthesis of a Carbon Analogue of Scytonemin

“…Tetramethylsilane (0.00 ppm) for compounds with a phenyl group or CHCl 3 (7.26 ppm) were used as an internal reference. 13 C-NMR spectra were measured with JNM-ECS400 or JNM-ECA600 spectrometers for samples in CDCl 3 . CDCl 3 (77.00 ppm) was used as an internal reference.…”

“…During our studies on the syntheses of various kind of alkaloids, [11][12][13][14][15][16][17][18][19] we became very interested in the highly conjugated and characteristic dimeric structure of scytonemin as well as its biological activity. We postulated that the origin of the biological activity of scytonemin (1) might be elucidated by comparison with its carbon analogue, in which two nitrogen atoms are replaced by two carbon atoms.…”

“…[5][6][7][8] Besides this important function, scytonemin exhibits a biological activity as a small molecule inhibitor of polo-like kinase 1 9) and possesses anti-inflammatory and antiproliferative properties. 10) During our studies on the syntheses of various kind of alkaloids, [11][12][13][14][15][16][17][18][19] we became very interested in the highly conjugated and characteristic dimeric structure of scytonemin as well as its biological activity. We postulated that the origin of the biological activity of scytonemin (1) might be elucidated by comparison with its carbon analogue, in which two nitrogen atoms are replaced by two carbon atoms.…”

Five‐Membered Carbocycles

“…129 Their strategy employed the use of two intramolecular PKRs to build a tetracyclic intermediate from acyclic starting material; diethyl L-tartrate. In the synthesis of (±)-pentalenene, the PKR was used to construct the angularly fused triquinane ring system 77 from cyclopentene 76.…”