An Efficient Synthesis of Tetrodotoxin

Tetrodotoxin (TTX) is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, and one of the most celebrated targets of synthetic chemistry. Here, we present a stereoselective synthesis of TTX that proceeds in 22 steps starting from a readily available glucose derivative. The central cyclohexane ring of TTX and its α-tertiary amine moiety was established via the intramolecular 1,3-dipolar cycloaddition of a nitrile oxide, followed by alkynyl addition to the resultant isoxazoline. After some carefully chosen protecting group manipulations, a ruthenium-catalyzed hydroxylactonization set the stage for the formation of its dioxa-adamantane core. Installation of the guanidine, oxidation of a primary alcohol, and late-stage epimerization of the resultant aldehyde gave a mixture of TTX and anhydro TTX. Our synthesis represents one of the most effective of TTX reported to date and could give ready access to biologically active derivatives.

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Oxazole-Based Compounds As Anticancer Agents

Current Medicinal Chemistry ◽

10.2174/0929867326666181203130402 ◽

2020 ◽

Vol 26 (41) ◽

pp. 7337-7371 ◽

Cited By ~ 3

Author(s):

Maria A. Chiacchio ◽

Giuseppe Lanza ◽

Ugo Chiacchio ◽

Salvatore V. Giofrè ◽

Roberto Romeo ◽

...

Keyword(s):

Cancer Research ◽

Drug Discovery ◽

Anticancer Agents ◽

Heterocyclic Compounds ◽

Chemical Diversity ◽

Biologically Active ◽

New Drugs ◽

The Core ◽

Anti Cancer ◽

Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

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N-[7-Chloro-4-[4-(phenoxymethyl)-1H-1,2,3-triazol-1-yl] quinoline]-acetamide

Molbank ◽

10.3390/m1213 ◽

2021 ◽

Vol 2021 (2) ◽

pp. M1213

Author(s):

Paolo Coghi ◽

Jerome P. L. Ng ◽

Ali Adnan Nasim ◽

Vincent Kam Wai Wong

Keyword(s):

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Quantum Coherence ◽

Biologically Active ◽

Proton Nuclear Magnetic Resonance ◽

Dipolar Cycloaddition ◽

Heteronuclear Single Quantum Coherence ◽

Pharmacokinetic Properties ◽

Nuclear Magnetic

The 1,2,3-triazole is a well-known biologically active pharmacophore constructed by the copper-catalyzed azide–alkyne cycloaddition. We herein reported the synthesis of 4-amino-7-chloro-based [1,2,3]-triazole hybrids via Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition of 4-azido-7-chloroquinoline with an alkyne derivative of acetaminophen. The compound was fully characterized by Fourier-transform infrared (FTIR), proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), heteronuclear single quantum coherence (HSQC), ultraviolet (UV) and high-resolution mass spectroscopies (HRMS). This compound was screened in vitro with different normal and cancer cell lines. The drug likeness of the compound was also investigated by predicting its pharmacokinetic properties.

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