Synthesis of DNA-Interactive Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs)

Abstract

2819 4.1. Synthesis of Pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones (PBD Dilactams) 2820 4.1.1. Cyclization of Methyl and Ethyl N-(2-Nitrobenzoyl)pyrrolidine-2-carboxylates 2820 4.1.2. Cyclization of Methyl N-(2-Azidobenzoyl)pyrrolidine-2-carboxylates 2822 4.1.3. Cyclocondensation of Isatoic Anhydrides with Substituted Prolines 2822 4.1.4. Cyclization of 1-Benzoyl-N-methoxypyrrolidine-2-carboxamides 2825 4.1.5. Cyclization of N-(2-Trifluoromethylsulfonyloxybenzoyl)pyrrolidine-2-carboxylic Esters 2825 4.2. Reduction of PBD Dilactams to PBD N10-C11 Carbinolamines/Imines 2826 5. Cyclization of Substituted N-Benzoylpyrrolidine Precursors 2828 5.1. Reductive Cyclization of N-(2-Nitrobenzoyl)pyrrolidine-2-carboxaldehydes 2828 5.2. Cyclization of N-(2-Aminobenzoyl)pyrrolidine-2-carboxaldehyde Diethyl Thioacetals 2830 5.3. Cyclization of N-(2-Aminobenzoyl)pyrrolidine-2-carboxaldehyde Dimethyl Acetals 2840 5.4. Cyclization of N-(2-Azidobenzoyl)pyrrolidine-2carboxaldehydes 2841 5.5. Oxidative Cyclization of N-(2-(Protected)aminobenzoyl)pyrrolidine-2methanol Precursors 2841 6. Oxidation of Cyclic N10-C11 Secondary Amines 2852 7. Solid-Phase and Parallel Syntheses of Pyrrolo[2,1-c][1,4]benzodiazepines 2853 8. Synthesis of N10-and C11-Substituted Pyrrolo-[2,1-c][1,4]benzodiazepines 2857

DNA sequence-selective C8-linked pyrrolobenzodiazepine–heterocyclic polyamide conjugates show anti-tubercular-specific activities

“…1,2 Therefore, new antibiotics with novel 47 a lesser extent than PBDs, as they lack the N10-C11 imine moiety responsible for the electrophilic 75 alkylation of the C2-NH2 of guanine bases, thus resulting in a non-covalent DNA interaction and 76 reduced antibacterial and anticancer potency. 9,20 77…”

Intramolecular Azide to Alkene Cycloadditions for the Construction of Pyrrolobenzodiazepines and Azetidino-Benzodiazepines

“…The pyrrolobenzodiazepines (PBDs), of which the natural products abbeymycin (1), DC-81 (2) and fuligocandin B (3) (Figure 1) are typical examples, are a class of molecule that has attracted significant OPEN ACCESS interest due the antitumour and antibiotic activity of several members [1][2][3][4][5]. Synthetic hybrids [5][6][7][8] and dimers [5,[9][10][11] have also shown significant biological activity and members of the dimer class have entered Phase II clinical development as antitumour compounds.…”

“…Synthetic hybrids [5][6][7][8] and dimers [5,[9][10][11] have also shown significant biological activity and members of the dimer class have entered Phase II clinical development as antitumour compounds. PBDs with additional fused rings such as the circumdatin (4) [12], bretazenil (5) [13] and the 1,2,3-triazolo-fused system 6 [14] are attractive as potential antitumour compounds, neurological agents, and protease inhibitors, respectively.…”

Biopolymer-supported iron oxide nanocomposite: Preparation and catalytic application in the synthesis of benzodiazepine derivatives

“…Owing to their versatile applications various methods for the synthesis of benzodiazepines have been reported. One of the commonly reported methods for the synthesis of benzodiazepines is the condensation reaction between o-phenylenediamines and ketones [5], enones [6] or β-haloketones [7], using ionic liquids [8], under microwave irradiation [9] [16]. The reported methods of the synthesis of benzodiazepine suffers from one or other limitations such as harsh reaction conditions, expensive reagents, low yields, relatively long reaction time and formations of side products [17][18][19][20][21][22][23][24][25].…”