Efficient protocol to quinazolino[3,2-d][1,4]benzodiazepine-6,9-dione via Staudinger-aza-Wittig cyclization: application to synthesis of Asperlicin D

Abstract

Tandem Staudinger and intramolecular aza-Wittig reactions followed by cyclodehydration of the ,4]benzodiazepine-6,9-dione ring system found in some biologically active natural alkaloids. This method was successfully implemented to synthesize asperlicin D from a linear peptide containing ester and azido terminal groups.

A combined experimental and theoretical study of the synthesis of quinazolino[3,2-a][1,5]benzodiazepin-13-ones

“…Naturally occurring alkaloids such as asperlicins, circumdatins, benzomalvins and sclerotigenin incorporating a quinazolino [1,4]benzodiazepine system in their structure have been isolated from different sources. 1 These alkaloids display various biological activities.…”

“…1 These alkaloids display various biological activities. In a quest to find additional potential quinazoline-based derivatives, various substituted quinazolinones 2,3 and compounds encompassing a quinazolino [1,4]benzodiazepine moiety in their skeleton [4][5][6][7] have been developed. As a part of our ongoing research activity, [8][9][10] we were interested in the synthesis of some quinazolino [1,5]benzdiazepine derivatives as possible analogues of natural products.…”

“…As a part of our ongoing research activity, [8][9][10] we were interested in the synthesis of some quinazolino [1,5]benzdiazepine derivatives as possible analogues of natural products. The main synthetic routes to compounds with quinazolino [1,4]benzodiazepine moiety utilize the implementations of 2-azidobenzoylamides in aza-Wittig methodology 4,5,11 and transition metal-…”

Novel synthesis of quinazolino[3,2-a][1,5]benzodiazepines: an experimental and computational study

“…15 Various methods for the synthesis of these alkaloids encompassing a quinazolino [1,4]benzodiazepine moiety in their skeleton have been developed and numerous research papers have recently appeared. 16,17 As part of our current studies on the development of efficient methods for the preparation of polycyclic 1,5-benzodiazepines we investigated the synthesis of quinazolino [1,5]benzodiazepines. 18,19 A wide range of novel 6,7-dihydroquinazolino[3,2-a] [1,5]benzodiazepinone derivatives were synthesized in a two-step method involving (i) benzoylation of variously substituted 1,3,4,5-tetrahydro-1,5-benzodiazepin-2-ones with 2-nitrobenzoyl chloride, and (ii) a metal induced reductive N-heterocyclization of the obtained 2-nitrobenzoylamides.…”