A Synthetic Overview of Benzoxazines and Benzoxazepines as Anticancer Agents

Abstract

Benzoxazines and benzoxazepines are nitrogen and oxygen‐containing six and seven‐membered benzo‐fused heterocyclic scaffolds, respectively. Benzoxazepines and benzoxazines are well‐known pharmacophores in pharmaceutical chemistry, which are of significant interest and have been extensively studied because of their promising activity against various diseases including their wide range of anticancer activity. Several reports are known for synthesizing benzoxazine and benzoxazepine‐based compounds in the literature. Herein this review provides a critical analysis of synthetic strategies towards benzoxazines and benzoxazepines along with various ranges of anticancer activities based on these molecules that have been reported from 2010 onwards. This review also focuses on the structure‐activity relationship of the benzoxazine and benzoxazepine scaffolds containing bioactive compounds and describes how the structural modification affects their anticancer activity.

Cинтез Нових Похідних Бензоксазину За Реакцією Віттіга

“…Похідні 1,4-бензоксазину (Chatterjee et al, 2023) отримують відновленням о-нітрофеноксиметилкетонів під дією плюмбум (II) хлориду. В більш жорстких умовах відновлення, наприклад з допомогою олова і хлоридної кислоти або при каталітичному гідруванні, отримують дигідропохідні (бензоксазинони).…”

Biocatalytic Generation of o-Quinone Imines in the Synthesis of 1,4-Benzoxazines and Its Comparative Green Chemistry Metrics

“…o -Quinone imines are transitory and highly reactive species that are versatile intermediates in organic synthesis . They readily undergo a variety of reactions, including 1,4-conjugate additions, 1,3-oxazole formation, and [4 + 2] inverse electron demand Diels–Alder cycloadditions (IEDDA). ,, The IEDDA reactions are of interest since they give rise to a 1,4-benzoxazine scaffold that is present in a variety of complex molecules including drug candidates, as well as approved medicines (e.g., azasetron and levofloxacin). − In this context, IEDDA reactions are particularly useful since their concerted reaction mechanism imparts good control of both regio- and stereochemistry in comparison to stepwise reactions , of forming benzoxazines.…”

“… 1 , 4 , 5 The IEDDA reactions are of interest since they give rise to a 1,4-benzoxazine scaffold that is present in a variety of complex molecules including drug candidates, as well as approved medicines (e.g., azasetron and levofloxacin). 6 − 8 In this context, IEDDA reactions are particularly useful since their concerted reaction mechanism imparts good control of both regio- and stereochemistry in comparison to stepwise reactions 9 , 10 of forming benzoxazines.…”

“…) 2 CO) δ 7.36 (d, J = 2.1 Hz, 1H), 7.30 (dd, J = 8.3, 2.1 Hz, 1H),6.80 (d, J = 8.3 Hz, 1H), 5.39 (d, J = 3.8 Hz, 1H), 4.28 (q, J = 7.1 Hz, 1H), 4.22−4.05 (m, 2H), 4.00 (ap q, J = 8.0 Hz, 2H), 2.10−2.25 (m, 1H), 1.80−1.90 (m, 1H), 1.33 (t, J = 7.1 Hz, 3H);13 C NMR (101 MHz, (CD 3 ) 2 CO) δ 165.9, 145.6, 131.8, 124.0, 119.5, 116.1, 115.3, 97.1, 67.4, 60.0, 53.7, 28.4, 13.8; m/z (ESI + ) 250 (MH + ); HRMS (APCI + ) C 13 H 16 NO 4 + (MH + ) requires 250.1073, found 250.1074, δ 0.4 ppm. Ethyl 2-Ethoxy-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylate, 3B.…”