Synthesis of adamantane derivatives. XXXII. The Beckmann rearrangement and fragmentation aptitude of noradamantan-2-one oxime

Tadashi. Sasaki; Shoji. Eguchi; Osamu. Hiroaki

doi:10.1021/jo00872a028

ChemInform Abstract: SYNTHESIS OF ADAMANTANE DERIVATIVES. XXXII. THE BECKMANN REARRANGEMENT AND FRAGMENTATION APTITUDE OF NORADAMANTAN-2-ONE OXIME

Chemischer Informationsdienst ◽

10.1002/chin.197638101 ◽

1976 ◽

Vol 7 (38) ◽

pp. no-no

Author(s):

T. SASAKI ◽

S. EGUCHI ◽

O. HIROAKI

Keyword(s):

Beckmann Rearrangement ◽

Adamantane Derivatives

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Beckmann rearrangement of adamantanone oxime as a route to ditopic and tritopic secondarily substituted adamantane derivatives

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19841774 ◽

1984 ◽

Vol 49 (8) ◽

pp. 1774-1779 ◽

Cited By ~ 2

Author(s):

Jan Tříska ◽

Luděk Vodička ◽

Eugenijus P. Butkus ◽

Milan Hájek

Keyword(s):

Silica Gel ◽

Hydrobromic Acid ◽

Nmr Spectra ◽

Hydroxylamine Hydrochloride ◽

Beckmann Rearrangement ◽

Adsorption Chromatography ◽

Adamantane Derivatives ◽

Acid Solutions ◽

Hydroiodic Acid ◽

Pure Substances

The reaction in mixtures of adamantanone with hydroxylamine hydrochloride was studied in hydrochloric, hydrobromic, and hydroiodic acid solutions. In hydrochloric and hydroiodic acids, mixtures of isomers of 4-chloroadamantan-2-one and 4-iodoadamantan-2-one, respectively, are formed, whereas in hydrobromic acid in the presence of excess hydroxylamine hydrochloride, three stereoisomers of 4,8-dibromoadamantan-2-one appear. All the stereoisomeric haloketones were isolated by elution adsorption chromatography on silica gel or by crystalization. For the pure substances, their infrared, mass, and NMR spectra were measured.

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Synthesis and Antimicrobial Activity of Adamantyl Substituted Pyridoxine Derivatives

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190911150705 ◽

2019 ◽

Vol 16 (12) ◽

pp. 1360-1369 ◽

Cited By ~ 2

Author(s):

Rail Khaziev ◽

Nikita Shtyrlin ◽

Roman Pavelyev ◽

Raushan Nigmatullin ◽

Raylya Gabbasova ◽

...

Keyword(s):

Influenza Virus ◽

Lipid Membranes ◽

Specific Activity ◽

Tuberculosis H37rv ◽

Microbial Pathogens ◽

Adamantane Derivatives ◽

Carbon Cage ◽

H37rv Strain ◽

Derivatives Of

Background: Adamantane derivatives possess multiple pharmacological activities such as antiviral, anticancer, antimycobacterial, antidiabetic, antiparkinsonian and others. The interest of medicinal chemists in adamantane compounds is due to their unique spatial structure, high lipophilicity, and carbon cage rigidity. As a result, these molecules can easily penetrate biological lipid membranes and often have unique target-specific activity profile. Another pharmacophore studied in this work is pyridoxine (vitamin B6). Pyridoxine plays highly important roles in living cells as a key cofactor of many enzymes. On the other hand, its molecular scaffold is a valuable structural platform which has led to the development of several launched drugs (Pyritinol, Pirisudanol, Cycletanine, Mangafodipir) and a wide number of preclinical and clinical drug candidates. Objective: The objective of this study is a synthesis of pyridoxine-adamantane and pyridoxinecyclooctane dipharmacophore molecules. The underlying idea was to assess the antibacterial and antiviral potential of such dipharmacophores, based on multiple examples of promising antiinfective agents which have in their structures adamantane and pyridoxine moieties. Another specific reason was to explore the ability of pyridoxine pharmacophore to suppress the potential of microbial pathogens to develop resistance to drug molecules. Methods: In this study, a series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkyl amines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. All synthesized compounds have been tested for their in vitro activity against M. tuberculosis H37Rv strain and H3N2 (A/Aichi/2/68) influenza virus. Results: Series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkylamines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. Reaction of cycloalkylamines with pyridoxine derivatives, in which meta-hydroxyl and ortho-hydroxymethyl groups are protected by acetyl groups, represents a useful alternative to reductive amination of aldehydes and nucleophilic substitution of alkyl halides. According to a tentative mechanism, it proceeds via paraand ortho-pyridinone methides which readily react with nucleophiles. None of the synthesized dipharmacophore compounds showed activity against M. tuberculosis H37Rv strain. At the same time, three compounds demonstrated some antiviral activity against H3N2 (A/Aichi/2/68) influenza virus (EC50 52-88 µg/mL) that was comparable to the activity of Amantadine, though lower than the activity of Rimantadine. The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane. Conclusion: The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane.

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