Synthesis of guaipyridine alkaloids (±)-cananodine and (±)-rupestines D and G using an intramolecular Mizoroki-Heck reaction

Guaiane sesquiterpenes from the gorgonian Echinogorgia flora collected in the South China Sea

“… 5 Potential bioactivity and rare existence of this kind of compounds in nature make it necessary to isolate new members with an effective method, although the synthesis of a similar type of these alkaloids has been reported. 6–8 As the analogues of guaipyridine, guaiane sesquiterpenes are widely distributed among marine organisms, including gorgonians, 9 soft corals, 10 sponges 11 and nudibranchs. 12 These marine-derived guaianes, mostly featured with the α,β-unsaturated-β-methyl-γ-lactone moiety, partly show inhibitory effects on the generation of superoxide anion, 13 antimicrobial, 14 antioxidant and cytotoxic activities.…”

Synthesis of Guaipyridine Alkaloids Rupestine M and L by Cycloaddition/Cycloreversion of an Intermediate 1,4-Oxazinone

“…3 [] D 20 -40 (c 0.03, MeOH)]. Because our synthesis started from a known chiral pool reagent [(-)-citronellal], our results suggest a revision of the absolute configuration of rupestine L (7) to that shown in Scheme 3. The assignment of natural rupestine L as (5S,8R) was made based on comparison of calculated and experimental CD spectra.…”

“…Cananodine (6) has the most recognized biological activity in the family and shows potent and selective anticancer activity against hepatocytes (IC 50 0.94 M, Hep G2 cells). 5 In part due to this bioactivity, 6 and other guaipyridines have attracted both synthetic attention [6][7][8][9][10][11][12] and renewed isolation efforts. 2,3,13,14 We viewed the guaipyridine scaffold as an instructive model to explore our interest in the de novo synthesis of pyridines by domino reaction processes.…”

“…[1][2][3][4] The cycloheptane ring displays variation in substitution and stereochemistry. The C5 methyl group is found in either absolute configuration; the C8 position presents diverse alkyl, alkenyl, acyl, or carboxyl substituents (e.g., 1-6), as well as hydroxyl substitution as shown in rupestine L and M (7,8). The relative stereochemical relationship between the C5 and C8 substituents may be syn or anti.…”

Enantioselective Synthesis of the Guaipyridine Alkaloid (+)- and (−)-Cananodine

“…1 H NMR (500 MHz, CDCl 3 ): δ 7.43 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 5.78 (dddd, J = 17.0, 10.3, 6.6, 6.6 Hz, 1H), 5.02 (app dd, 1H), 4.97 (app dd, 1H), 3.65 (s, 3H), 3.22 (dd, J = 14.8, 8.8 Hz, 1H), 3.09−3.04 (m, 1H), 3.00 (dd, J = 14.9, 5.1 Hz, 1H), 2.51 (s, 3H), 2.16−2.05 (m, 2H), 1.76 (app sextet, 1H), 1.67−1.60 (m, 1H) ppm. 13 (8). In a doublenecked flask, K 2 CO 3 (0.300 g, 2.17 mmol) and Pd(PPh 3 ) 4 (5 mol %, 0.026 g, 0.023 mmol) were added and put under Ar.…”