Synthesis and cholinesterase inhibitory activity study of Amaryllidaceae alkaloid analogues with <i>N</i>-methyl substitution

Jansa, Petr; Barvı́k, Ivan; Hulcová, Daniela; Matoušová, Eliška

doi:10.1039/d2ob00553k

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…Furthermore, several crucial interactions also have been reported in numerous studies over the past 5 years. Particularly, the pi‐pi shape interactions with TRP279, TRP84, and PHE330, as well as hydrogen bonding with PHE288 and ARG289, have been highlighted (Jansa et al., 2022; Qi et al., 2023; Zahedi et al., 2023). However, none of the active compounds obtained from the in vitro study were found to fit within the active site using either standard or extra precision methods.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, and evaluation of novel bistrifluoromethyl‐based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease

Dincel,

Başoğlu‐Ünal,

Kuran

et al. 2024

Chem Biol Drug Des

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In this project, non‐sulfonamide bistrifluoromethyl‐derived hydrazide‐hydrazones were synthesized as multi‐target‐directed ligands to treat Alzheimer's disease and then, the novel derivatives were characterized by diverse spectral methods. Acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) inhibitory qualifications of these compounds were determined. The reported compounds (2a‐y) were determined to be effective inhibitors of the hCA I, hCA II and AChE enzymes with Ki values in the range of 1.130 ± 0.15–5.440 ± 0.93 μM for hCA I, 0.894 ± 0.05–6.647 ± 1.35 μM for hCA II, and 0.196 ± 0.03–4.222 ± 1.04 μM for AChE. In silico studies were also performed to illuminate the binding interactions.

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Section: Resultsmentioning

confidence: 99%

Design, synthesis, and evaluation of novel bistrifluoromethyl‐based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease

Dincel,

Başoğlu‐Ünal,

Kuran

et al. 2024

Chem Biol Drug Des

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“…Its hydroxyl immediately attacked the ketone group and formed a very stable hemiacetal 5 that resisted further reduction (Scheme 3). Product 5 was then subjected to the Boc cleavage with ZnBr 2 and methylation using our previously optimised method, [22] which resulted in a moderate yield of a five‐membered tazettine analogue 6 .…”

Section: Resultsmentioning

confidence: 99%

Oxidative Cleavage and Ring Reconstruction for the Synthesis of Amaryllidaceae Alkaloid Analogues

Jansa,

Císařová,

Matoušová

2023

Eur J Org Chem

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This study presents the synthesis of analogues of bioactive Amaryllidaceae alkaloids that contain a five‐membered ring C and a quaternary carbon centre. The synthesis was carried out in a divergent manner, starting from a common intermediate, keto aldehyde 1 a. This intermediate was obtained by oxidative cleavage of a carbocyclic ring present in the previously synthesised tetracyclic compounds. Subsequent closure of a new heterocyclic ring B using different methods led to products with structural cores found in naturally occurring alkaloids such as pretazettine, tazettine or macronine. In addition, an analogue of egonine was prepared from the same intermediate. Our approach thus provides access to multiple structural types of potentially bioactive molecules.

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“…In 2022, polycyclic compounds bearing N-methyl substitution were generated using Boc as the protected group with excellent enantiomeric excess by Matousova group (Scheme 40). [65] In 2016, Hodgson group reported a β-iodo Morita-Baylis-Hillman reaction to synthesize (Z)-iodo ester, followed by Sonogashira cross-coupling-5-exo-dig lactonization to produce (Z)-γ-alkylidenebutenolide (Scheme 41a). [66] In the following year, the same group expanded the scope of the reaction (Scheme 41b).…”

Section: Reaction With Alkynementioning

confidence: 99%

“…In 2022, polycyclic compounds bearing N‐methyl substitution were generated using Boc as the protected group with excellent enantiomeric excess by Matousova group (Scheme 40). [65] …”

Section: Reaction With Alkynementioning

confidence: 99%

Transition‐Metal‐Catalyzed Cyclization of Alkenyl Iodide

Jia,

Liu,

Xie

et al. 2023

Adv Synth Catal

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Alkenyl iodide, as an essential precursor and structural unit in organic synthesis, has been widely used in the synthesis of natural products, pharmaceutical pesticides and functional materials. The high reactivity of Csp2‐I bond allowing could lead to form C‐M bond via oxidative addition, and then undergoes C‐M bond transformations to construct new chemical bonds. A variety of valuable scaffolds, in particular the cyclic motifs, could be achieved via designing and synthesis the corresponding alkenyl iodide, which makes this strategy to be a hot topic in synthetic chemistry. In this paper, the recent progress of transition metal‐catalyzed cyclization of alkenyl iodides is summarized, and the possible mechanisms for most transformations are described in detail.

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Synthesis and cholinesterase inhibitory activity study of Amaryllidaceae alkaloid analogues with N-methyl substitution

Abstract: Polycyclic compounds with N methyl substitution, structurally related to Amaryllidaceae alkaloids, have been synthesised, together with their analogues bearing a quaternary nitrogen atom. To prevent the lone electron pair of...

Cited by 7 publications

References 28 publications

Design, synthesis, and evaluation of novel bistrifluoromethyl‐based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease

Design, synthesis, and evaluation of novel bistrifluoromethyl‐based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease

Oxidative Cleavage and Ring Reconstruction for the Synthesis of Amaryllidaceae Alkaloid Analogues

Transition‐Metal‐Catalyzed Cyclization of Alkenyl Iodide

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