A New Acyl Radical-based Route to the 1,5-Methanoazocino[4,3-b]indole Framework of Uleine and Strychnos Alkaloids

Abstract

C-4 or C-12 ethyl substituted 1,5-methanoazocino[4,3-b]indoles, which constitute the tetracyclic framework of uleine alkaloids as well as the ABDE substructure of the Strychnos alkaloid family, have been synthesized by novel 6-exo and 6-endo cyclizations of selenoester-derived 2-indolylacyl radicals upon 5-ethyl-1,2,3,6- and 3-ethyl-1,2,5,6-tetrahydropyridines, respectively.

New Route to 20-Deethyldasycarpidone by Ring-Closure with DDQ

“…Compounds such as dasycarpidone and 20-deethyl-4-demethyldasycapidone possess the tetracyclic ring system of the Strychnos indole alkaloids 2,3 and one such alkaloids, 20-deethyldasycarpidone (8) is of great pharmaceutical interest. Several total synthesis of 8 have been reported previously.…”

“…Several total synthesis of 8 have been reported previously. 4,5 All routes for the construction of the 20-deethyldasycarpidone (8), 6 (±)-isodasycarpidone, 7 dasycarpidone 8 and 20-deethyl-4-demethyldasycarpidone 9,10 start with 2-cyano-1,2,3,6-tetrahydropyridine 9 or involve the reaction of indolemagnesium bromide with methyl 3-ethylisonicotinate N-oxide. 11 The azocino [4,3-b]indole motif is also found as a key feature in other Strychnos, alkaloids, such as akuamicine, tubifolidine, etc.…”

Rongalite®/PEG-400 as reducing system in the synthesis of new glycerol-derived selenol esters using anhydrides and bis-(2,2-dimethyl-1,3-dioxolanylmethyl)diselenide as substrates

“…They have been used as precursors of acyl radicals and anions, [1][2][3][4] intermediates in the synthesis of ketones, 5,6 as building blocks of heterocyclic compounds, 7 in Diels-Alder, 8,9 cyclocondensation 10 and various cyclization reactions. [11][12][13][14] They were also used as a precursors in the synthesis of vinyl compounds, 15 in the formation of C-peptide bonds, [16][17][18] and the synthesis of some natural occurring compounds, [19][20][21][22][23] besides having proven antioxidant properties.…”

Facile synthesis of the azocino[4,3-b]indole framework of strychnopivotine and other Strychnos alkaloids

“…1). [1][2][3][4][5][6] Therefore, many investigations have been devoted to the synthesis of tetracyclic 1,5-methanoazocino [4,3-b]indole skeleton. [7][8][9][10][11] The biological activities of these compounds make them of a great pharmacological interest, resulting in sustained efforts in the development of methods for their preparation.…”

“…The most characteristic absorptions of the 1 H NMR spectrum of compound 6 are singlets at 5.77 and 5.94 ppm for the methine proton at C-1 position which is comparable to the data observed previously for an analogous methanoazocino[4,3-b] structure. 6,34,44 In the final step, the treatment of hydroxy compound 6 with triethylamine and methanesulfonyl chloride was followed by the reduction of the resulting intermediate mesylate with zinc dust in acetic acid to give product 7. The structure of compounds 6 of 7 was confirmed by 2D NMR spectroscopy ( 1 H-1 H COSY, 1 H-13 C HSQC, and NOESY) experiments.…”