New polycyclic ring systems derived from canthin‐4‐one

Abstract

Starting from 5,6‐dihydrocanthin‐4‐one, new penta‐ and hexacyclic ring systems (1,7b,14‐triazadi‐benzo[e,k]acephenanthrylenes, 1,7b,10,12‐tetraazabenzo[e]acephenanthrylenes) were built up using ring annelation reactions. The new compounds represent hybrids between the canthinones and several bioactive aromatic alkaloids J. Heterocyclic Chem., (2010).

New approaches to the synthesis of canthin-4-one alkaloids and synthetic analogues

“…The '1,3-diketone route' starting from 1-acetyl-b-carboline (5) and utilizing N-acylbenzotriazoles (6a/6b) as acyl donors is limited to the synthesis of canthin-4-ones bearing small alkyl substituents at C-6, namely the alkaloids norisotuboflavine (1a) and isotuboflavine (1b). The 'isoxazole route', starting with a 1,3-dipolar cycloaddition of readily available 1-ethynyl-b-carboline (8) with nitrile oxides, followed by reductive opening of the isoxazole ring and thermal cyclization, gave the desired 6-substituted canthin-4-ones 1aec in high overall yields.…”

“…18 The required 1-ethynyl-b-carboline (8) was obtained in excellent yield by Sonogashira coupling 26 of 1-bromob-carboline (7) with (trimethylsilyl)acetylene, followed by K 2 CO 3 -mediated desilylation. 27 Alkyne 8 was converted to the isoxazoles 9aec by cycloaddition with nitrile oxides, which in turn were prepared in situ by treatment of the oximes of acetaldehyde, propionaldehyde, and benzaldehyde with N-chlorosuccinimide (NCS).…”

“…We also investigated, whether 5,6-disubstituted canthin-4-ones are accessible with this protocol. For this purpose condensation of 1-butanoyl-b-carboline (4b) 7 with N-acetylbenzotriazole (6a) was attempted. This experiment was unsuccessful, demonstrating another limitation of the 1,3-diketone route.…”

“…6 Further, canthin-4-ones were used as intermediates for the synthesis of antimicrobial polycyclic compounds. 5,7 Ring transformation reactions of canthin-4-ones with guanidinium salts give 1-(2-aminopyrimidin-4-yl)-b-carbolines, e.g. the anxiolytic alkaloid annomontine, 8,9 and its antimalarial analogue C-117.…”

“…4 Significant antimicrobial activities have been shown for the parent canthin-4-one and some of its derivatives. 5 Synthetic canthin-4-ones exhibit phosphodiesterase-inhibitory activity. 6 Further, canthin-4-ones were used as intermediates for the synthesis of antimicrobial polycyclic compounds.…”