Indole‐Fused Epoxy‐1,5‐Diazocines as Cancer‐Selective Cytotoxic Agents

Abstract

Dimerization of 2‐(diformylmethylene)‐3,3‐dimethylindole by the action of tosyl chloride (TsCl) led to the creation of an epoxy‐[1,5]‐diazocine bicycle. The structure of the molecule resembles that of the naturally occurring C‐curarine‐I. The molecule shows significant cytotoxicity against cancer lines MCF‐7 and MDA‐MB‐231, but not toward the normal cell line CCD‐841. A series of substituted 2‐(diformylmethylene)‐3,3‐dimethylindoles was accordingly dimerized, and the products were studied for their cytotoxic activities.

Epoxydibenzo[b,f][1,5]diazocines: From a Hidden Structural Motif to an Efficient Solvent-Free Synthetic Protocol

“…Unfortunately, these structurally complex heterocycles are isolated in low yields (15a-d, 9-28%). In 2017, Khaledi and co-workers 22 employed a similar synthetic strategy (Scheme 4). Treatment of 1,3-dialdehyde 16 with NaOH and TsCl afforded epoxy [1,5][b,f]diazocines 17 in moderate to good yields, depending on the substitution pattern of the arene scaffold (17a-e, 54-86%).…”

Synthetic strategies and diversification of dibenzo[1,5]diazocines

“…Dibenzo [1,5]diazocines were first synthesised in 1896 1 and derivatives are categorised as eight-membered heterocycles comprising two nitrogen atoms at the 1,5-positions. These derivatives bear a close resemblance to Tröger's base which is of particular interest as a building block for supramolecular chemistry.…”

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Dibenzo [1,5]diazocine scaffolds are present in a wide range of organic building blocks, for example in pharmaceuticals, materials and structural chemistry. However, the development of these structural frameworks has not received significant attention owing to limited synthetic protocols and strategies.

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“…However, the development of these structural frameworks has not received significant attention owing to limited synthetic protocols and strategies. Herein, a summary of the attractive synthetic approaches for the construction of dibenzo[1,5]diazocines, epiminodibenzo[1,5]diazocines and epoxydibenzo [1,5]diazocines developed over the past two decades is presented. The spectroscopic, synthetic mechanisms for the formation of the heterocyclic rings and remarkable structural features, including in the solid-state, are discussed.…”

Synthesis of novel pyrazolo[3,4-b]pyridine derivatives in aqueous medium

“…Previous examples of the use of 2-(3,3-dimethyl-3H-indol-2-ylidene)malondialdehydes for heterocycle construction. [6][7][8][9][10][11][12][13][14][15] Fused heterocycles containing pyrazolopyridine systems have been associated with several biological and medicinal activities. organic synthesis and numerous studies have been reported due to their well-documented biological activity.…”