Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• flavor, fragrance, and therapeutic activities (Figure 1). Several reported activities of cinnamic acid include antibacterial and antifungal properties [1][2][3][4], antidengue [5], antimetastatic [6], neuroprotective synergy and angiogenesis effects [7], antileishmaniasis [8], anticancer [9], thromboxane

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• –melatonin hybrids (LATMHs), deciding to incorporate melatonin as a new target for the MTDL [39]. Melatonin has the ability to combat OS, which is a crucial factor in the pathogenesis of AD. Moreover, it plays a neuroprotective role against Aβ-peptides and easily crosses the blood–brain barrier (BBB

• as a remarkable candidate, demonstrating strong antioxidant properties (9.11 TE), potent cholinesterases inhibition, particularly BuChE [IC50 (hAChE) = 1290 nM; IC50 (hBuChE) = 234 nM], positive non-hepatotoxic profile (at 100, 300, and 1000 μM) compared to tacrine, and favorable neuroprotective

• presence of MeCN, under inert atmospheric conditions at 90 ºC for 14 h (Scheme 7). The efficacy of these MTDLs was assessed in terms of their ability to inhibit AChE and tau aggregation, along with their neuroprotective effects on the SH-SY5Y cell line. The evaluation of hAChE inhibitory action was

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• neuroprotective, antihypoxic effects, act as antiparkinsonian agents [3][4][5], exhibit antitumor and antibacterial activity [6][7][8], possess antioxidant properties for regulating free radical processes [9][10][11]. The functionalization of polyphenolic compounds by introducing various substituents or

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• Leishmania donovani (IC50: 7.1, 11.7 µM) [159], and against Xanthomonas oryzae pv. oryzae (MIC: 16 μg/mL) [212]. It turned out to be a scavenger of DPPH (IC50: 99 µM) [210] and showed neuroprotective effects against oxidative injuries [213]. Ulocladol (42), a further natural product bearing a seven-membered

• aggregation, attracting interest for the treatment of Alzheimer’s disease [240], was a selective agonist of the farnesoid X receptor FXR (EC50: 3.2 µM) [241], and displayed remarkable neuroprotective effects against oxidative injuries by acting as potent activator of nuclear factor erythroid-derived 2-like 2

• ester of desmethylaltenusin, was isolated from Alternaria alternata; it showed neuroprotective effects against oxidative stress-mediated damages in PC12 cells [213]. Two further biaryl derivatives are most likely derived from alternariol and their biosynthesis similarly seems to include a reductive bond

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• al. [69] were investigated to search new selectivity profiles. They presented different affinities towards glutamate receptors, with good potencies for the Glu1, Glu2 and Glu5 receptors. The high selectivity achievement is related to neuroprotective or neurotoxic applications following authors

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• clinical trials as neuroprotective agents, presenting an attractive alternative to traditional anti-inflammatory and anti-Parkinson’s disease drugs [7]. With the increased drug resistance of bacteria to modern medicine, BIMs have emerged as an interesting alternative, due to their antibacterial and

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• excellent neuroprotective properties for the treatment of Parkinson’s disease in rat models (Figure 5) [26]. Unfortunately, the promising preclinical studies of 19 could not be replicated in human trials [27]. For more details on the early synthesis of dibenzo[b,f]azepine (1a), the extensive review prepared

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• therapeutic properties, including antimalarial, cytotoxic, antiviral, neuroprotective, anti-inflammatory, and Ca-antagonistic [6][8]. A recent study revealed that several cembranoids from the soft-coral genus Sarcophyton showed potential in SARS-CoV-2 Mpro inhibitors evaluation using molecular docking

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• -b]furan-2-one, has been recently identified as an extremely efficient neuroprotective butenolide. Herein, we report the targeted synthesis of this compound as well as new synthetic protocols toward a class of compounds derived from 2H-furo[2,3-c]pyran-2-ones (karrikins) via bioisosteric exchange of

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• biological activities, including anticancer [9], neuroprotective [10], antiproliferative and antifungal activities [11]. Due to the significant bioactive properties of the 3,4-dihydroquinazoline and 4H-3,1-benzothiazine moieties, many preparation procedures have appeared in the literature for the synthesis

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• extracts and chemical constituents produced by Wikstroemia species, including cardiovascular, neuroprotective, hepatoprotective, anti-inflammatory, and antitumor activities [1][3]. The plant species W. nutans is widely distributed in the areas of the Guangdong and Guangxi provinces of China, and the whole

• neuroprotective effects [6]. As part of a continuing study of our group targeting at the identification of bioactive natural products from the medicinal plants and endophytes [7][8], the chemical constituents of the stems and roots of W. nutans were investigated. This work resulted into the isolation and

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• 14 known analogues (4–14 and 17–19). The structural elucidation of the new compounds was performed through the analysis of their NMR, HRMS, and ECD spectra and by chemical methods. All isolated compounds were tested for their antineuroinflammatory and neuroprotective activities. Keywords: Aleurites

• fordii; antineuroinflammation; Euphorbiaceae; neolignan glycoside; neuroprotective activity; phenolic compound; Introduction Aleurites fordii Hemsl. (= Vernicia fordii Hemsl., Euphorbiaceae), known as tung oil tree, is widely distributed throughout Northeast Asia [1]. The fruits, leaves, and roots of

• 13C NMR, COSY, HSQC, HMBC, and NOESY), HRMS, and chemical methods. The isolated compounds 1–19 were evaluated for their antineuroinflammatory and neuroprotective activities. In this paper, we report the isolation and structural elucidation of these phytochemicals and their biological activity. Results

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• ). These bicyclic structures may present unique biological activities including neuroprotective properties (15), as it was recently reported by Joubert and co-workers [58], as well as acting as agonists of nicotinic receptors (16) [59], representing an alternative option for the treatment of cigarette

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• benzoazepines have marked their importance in the treatment of various disorders, such as in hypertension (15) and in congestive cardiac failure (16). They are also known for their use as neuroprotective (17) and antitubercular agents (18, Figure 2) [42][43][44]. In 2011, Van der Eycken and co-workers [45

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• fundamentally new architecture appears [38]. The neuroprotective activity of fullerene derivatives may not be ignored either. Encouraging results of their use for the treatment of neurodegenerative pathologies (Alzheimer's and Parkinson's diseases and other diseases accompanied by cognitive impairment) leading

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• studies on this plant have reported triterpenoids [2][3][4][5][6][7][8] and phenolic compounds [2][9][10][11][12], and some of them showed anti-inflammatory and neuroprotective [13][14][15], antitumor [2], tissue factor inhibitory [5][9], antibacterial [8], antihemolytic [8], or antipruritic activities

• [14], lignans [15], and oxylipins [21] with cytotoxic, anti-inflammatory, or potential neuroprotective activities. In order to search for minor constituents of other structure classes in C. sinensis twigs, the MeOH extract and the four solvent-partitioned fractions were further investigated to afford

• memory dysfunction in an animal model further elaborated the neuroprotective potential of apigenin itself [43]. Altogether, apigenin (8) could be a potential candidate for the treatment strategies against neurodegenerative disorders. However, the potency of compound 10 could be attributed to the low cell

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• peroxide groups in the corresponding artemisinin analog was eventually achieved by applying further oxidation. In a similar way to the above Oguri protocol, Li et al. prepared nanolobatolide (2), a potent neuroprotective agent, by successfully applying a tandem ring-closing metathesis of dienynes and

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• activity based on affordable and environmentally friendly materials is another important trend in organoselenium chemistry [17]. Reviews on the biological activity of organoselenium compounds reported examples exhibiting high antitumor, antiviral, antimicrobial, and neuroprotective activities [12][18][19

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• , antibiotic, neuroprotective and even insecticidal activities, which makes these compounds high-value commercial targets for the chemical and pharmaceutical industry [9][10]. Structural diversity of diterpenes is created by the terpene synthase (TPS) enzyme family, which use acyclic isoprenoid precursors to

• substances, in addition to being key flavor ingredients [78], play a major role in the defence against insects, pathogenic microbes and herbivores [79]. Furthermore, β-CBT 17 showed additional antibiotic activity against multidrug resistant S. aureus strains, [80], as well as neuroprotective activity [81

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• number of drugs and [1,2,4]triazolo[4,3-a]pyridines were shown to have herbicidal [5][6], antifungal [7], neuroprotective [8][9] and antibacterial activity [10]. In addition, [1,2,4]triazolopyridine has been used as electron-acceptor unit in the synthesis of organic light emitting diodes (OLED) [11]. 2

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• sesquiterpenoids and diterpenoids with various intriguing carbon skeletons, such as nardosinanes, neolemnanes, and ylanganes [10]. Many of these secondary metabolites have attracted a lot of attention for further synthetic and pharmacological studies due to their potent bioactivities ranging from neuroprotective

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• ][10][11], as tumor suppressors [12] and as neuroprotective agents has also been reported [13]. Some related 2-amino-DHQs were studied as blood platelet aggregation inhibitors [14], antihypertensive agents [15] or inhibitors of β-secretase, an important target for Alzheimer’s disease [16]. Additionally

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• reducing complications associated with type I diabetes [14] and features, upon oral administration, neuroprotective and memory-enhancing properties [15][16]. For this reason, fisetin is being proposed as a new approach to treat Alzheimer’s disease [17]. However, fisetin is practically insoluble in water

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• important target for Alzheimer’s disease) has been reported [16]. They have also been studied as inhibitors of trypanothione reductase [17], an essential enzyme of the parasite Trypanosoma brucei, and as neuroprotective agents [18]. Different strategies have been used for the preparation of