Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• microwave reactor with LCMS analysis, selecting for high conversion and minimal reaction time (Table 1). While high heat was originally feared to cause side reactions due to possible lability of the Fmoc and internal cyclization to form a piperazinone [39], it was discovered that the monomer was stable up

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• piperazinone ring. Keywords: benzodiazepine; click reaction; multicomponent reaction; one-pot; piperazinone; polycyclic; triazole; tetrazole; Ugi–azide reaction; Introduction Triazole, tetrazole, and benzodiazepine are privileged heterocyclic rings commonly found in drug molecules and functional materials [1

• heterocyclic scaffolds to obtain biologically interesting compounds (Scheme 1) [35][36][37][38][39][40][41]. The development of methods for the synthesis of triazole, tetrazole, piperazinone, and 1,4-benzodiazepine motifs are attractive from both synthetic and medicinal chemistry considerations [42][43][44][45

• ]. We herein propose a one-pot synthesis involving an Ugi–azide 4-component (4-CR) reaction followed by lactamization and azide–alkyne cycloaddition for assembling triazole-fused and tetrazole-tethered 1,4-benzodiazepines 7 and triazole-, tetrazole-, and piperazinone-fused 1,4-benzodiazepines 8 (Scheme

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• strategies to easily generate multiple fused nitrogen heterocycles including benzodiazepinone and piperazinone cores. Keywords: arylglyoxals; deactivated amines; nitrogen heterocycles; Ugi reaction; Introduction Nitrogen heterocycles such as piperazines or diazepines represent important systems in the

• choice [23]. Synthesis of piperazinones On the basis of these results, we planned to synthesise piperazinone derivatives following a similar strategy. Thus, we chose different deactivated 2-amino-substituted carboxylic acid derivatives such as the indole-2-carboxylic acid, recently used in a similar

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• 873 million) [40]. It looks unlikely that this target will be met, thus the development of new potent anthelmintic drugs that act via novel mechanisms of action are urgently needed. Current anthelmintics – schistosomiasis Praziquantel (PZQ, 5), an N-acylated tetrahydroisoquinoline-piperazinone

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• active towards chronic diabetic complications including neuropathy, nephropathy, cataracts and retinopathy [13][14]. On the other hand, piperazinone condensed tetrahydroisoquinolines (THIQs) are widespread in nature with interesting biological activities [15]. They are also found to be building blocks

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• of 3-phenylproline, mono- or bicyclic piperazinone derived cores (conformationally constrained mimics of the Phe7–Phe8 linkage) afforded the non-natural peptides. These compounds displayed their amino acid residues in similar conformations to the receptor bound conformation of substance P. The three

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• unambiguously assigned by single crystal X-ray diffraction but the spectroscopic data did not match those reported for the natural product. The structure of the natural product must therefore be revised. Keywords: alkaloid; aza-Henry; natural products; nitro-Mannich; piperazinone; stereoselective synthesis

• [56]. Further stereochemical proof was provided by a single crystal X-ray structure determination of 2·HCl (vide infra). We presumed again that the primary amine of 21 would be more nucleophilic towards a keto acid derivative 5. In order to obtain a piperazinone of the desired connectivity (23) a keto

• oxalyl chloride (2.00 equiv) and catalytic DMF. Subsequent reaction with diamine 21 in the presence of pyridine (1.20 equiv) and catalytic DMAP over 24 h, according to previously reported reactions for similar keto acids [49], gave only the bis-adduct 24 and none of the desired piperazinone 23. By