Synthesis of cananodine by intramolecular epoxide opening

Abstract

Cananodine is a guaipyridine alkaloid with activity against liver cancer. Cananodine was synthesized using a remarkable intramolecular opening of a trisubstituted epoxide as the key step in construction of the seven-membered carbocycle of the target. The epoxide opening strategy allows all four stereoisomers of cananodine to be prepared.

Synthesis of natural ether lipids and 1-O-hexadecylglycero-arylboronates via an epoxide-ring opening approach: Potential antifouling additives to marine paint coatings

“…Regioselective and stereoselective epoxy-ring opening reactions are widely employed as important tools on the synthesis of natural products with biological activities [24,25,26]. We observed herein that in all epoxy-ring opening using the O-alkyl-glycidyl esters (4, 5, 6) as starting materials in the presence of aryl boronic acids using dioxane as solvent, and catalyzed by BF3.O(C2H5)2, only products (7-7f, 8, 9) with the configuration syn (I) were formed.…”

Total synthesis of rupestine G and its epimers

“…Another strategy was to build the seven-membered ring of guaipyridine compounds using derivatives of pyridine as the starting material. Applying this strategy, the Vyvyan group explored a base-promoted epoxide-opening and an intramolecular Heck cyclization to build the guaipyridine core ( scheme 2 ) [ 10 – 12 ]. This approach subtly uses cheap and commercially available chemicals to launch the synthesis and deserves to be further developed.…”

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

“…Cananodine ( 6 ) has the most recognized biological activity in the family and shows potent and selective anticancer activity against hepatocytes (IC 50 0.94 μM, 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…”

“…[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.…”

“…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.…”