Adamantane Nucleus Research Articles

Biophysical Evaluation and In Vitro Controlled Release of Two Isomeric Adamantane Phenylalkylamines with Antiproliferative/Anticancer and Analgesic Activity.

The aqueous dissolution profile of the isomeric synthetic adamantane phenylalkylamine hydrochlorides I and II was probed. These adducts have shown significant antiproliferative/anticancer activity associated with an analgesic profile against neuropathic pain. They are both devoid of toxic effects and show appreciable enzymatic human plasma stability. The structures of these two compounds have been elucidated using 2D NMR experiments, which were used to study their predominant conformations. Compound II’s scaffold appeared more flexible, as shown by the NOE spatial interactions between the alkyl bridge chain, the aromatic rings, and the adamantane nucleus. Conversely, compound I appeared very rigid, as it did not share significant NOEs between the aforementioned structural segments. MD simulations confirmed the NOE results. The aqueous dissolution profile of both molecules fits well with their minimum energy conformers’ features, which stem from the NOE data; this was nicely demonstrated, especially in the case of compound II.

Searching for novel applications of the benzohomoadamantane scaffold in medicinal chemistry: Synthesis of novel 11β-HSD1 inhibitors

The structural and physicochemical properties of the adamantane nucleus account for its use as a chemical scaffold in multiple drugs. In the last years, we have developed new polycyclic scaffolds as surrogates of the adamantane group with encouraging results in multiple targets. As adamantane is a common structural feature in several 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors, we have explored the ability of the 6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethanobenzo[9]annulen-7-yl scaffold to act as a surrogate of the adamantane nucleus in a novel series of 11β-HSD1 inhibitors. Of note, within this family of compounds one derivative is endowed with submicromolar 11β-HSD1 inhibitory activity. Molecular modeling studies support the binding of the compounds to the active site of the enzyme. However, a fine tuning of the hydrophobicity of the size-expanded nucleus may be beneficial for the inhibitory potency.

ChemInform Abstract: Ketoesters and Ketoacids of the Adamantane Series: Synthesis and Transformations

AbstractReview: 105 refs.

Rigid Multivalent Scaffolds Based on Adamantane

We present two new synthetic strategies to rigid multivalent scaffolds of the general structure 1 based on adamantane. Both routes start from arylated adamantane derivatives and give the target compounds 12 and 18 in 5 and 7 steps, respectively. These scaffolds have been designed for the assembly of multivalent binders for cell surface epitopes. The adamantane nucleus exposes three carboxylic acid groups in a well-defined tripodal geometry for conjugation of targeting ligands. In addition, an amino group at the fourth bridgehead position provides a flexible linker for attachment of effector molecules such as contrast agents, radiotracers, or cytotoxins without interfering with the cell binding process.

2‐(Adamantan‐1‐yl)imidazo[1,2‐a]pyridines and Their Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

2-(Adamantan-1-yl)imidazo[1,2-a]pyridines and Their Derivatives

A series of 1-adamantylimidazo[1,2-a]pyridines has been synthesized. The negative influence of electron-acceptor substituents in the pyridine ring on the alkylation of substituted 2-aminopyridines with bromomethyl (adamantan-1-yl) ketone has been demonstrated. Bromination of adamantylimidazo-[1,2-a]pyridines on boiling in liquid bromine or in the presence of a Lewis acid resulted in insertion of a bromine atom in the imidazole ring without affecting the adamantane nucleus. The compounds studied take part in the Ritter reaction despite the absence of an easily removed groups in the adamantane nucleus.

ChemInform Abstract: Synthesis, Antitumor Activity, and Anti‐HIV‐1 Testing of Certain Heterocyclic Systems Containing an Adamantane Nucleus.

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Synthesis and reactivity of aldehydes of the adamantane series

1-Adamantanecarbonitriles are very active in the Stephen reaction, which allows synthesis of the corresponding aldehydes in high yields. Electron-acceptor substituents in the 3 position of the adamantine nucleus exert almost no effect on the yield of aldehydes. Separation of the nitrile group and the adamantane nucleus by one methylene group results in a complete loss of reactivity. A quantitative study of the reactivity of the synthesized aldehydes in the oximation reaction was performed.

Synthesis, antitumor activity, and anti-HIV-1 testing of certain heterocyclic systems containing an adamantane nucleus.

A new series of substituted 2-(1-adamantyl)-4H-3,1-benzoxazin-4-ones and 2-(1-adamantyl)-3-amino or alkyl-3,4-dihydroquinazolin-4-ones have been synthesized and tested for their antitumor and antiviral activities. Among the tested compounds, compounds 5a and 5b exhibited a broad spectrum antitumor activity with full panel (MG-MID) median growth inhibition (GI50) values of 3.2 and 4.9 microM respectively. Meanwhile, compounds 5c, 5d, 5h, 5i, and 5j showed moderate selectivity towards leukemia cell lines. On the other hand, compounds 4a and 4b possessed moderate Anti-HIV-1 potency with EC50 values of 50.3 and 69.2 microM respectively. Detailed synthesis, spectroscopic, and biological data are reported.

Synthesis, Antitumor Activity, and Anti-HIV-1 Testing of Certain Heterocyclic Systems Containing an Adamantane Nucleus

Synthesis, Antitumor Activity, and Anti-HIV-1 Testing of Certain Heterocyclic Systems Containing an Adamantane Nucleus

Synthesis of totally chiral, multiple armed, poly Glu and poly Asp scaffoldings on bifunctional adamantane core

Three successive generations of peptidic scaffoldings consisting of two, six and fourteen chiral (all L) centres and four, eight and sixteen carbomethoxy groups, respectively, at the periphery with adamantane nucleus as the central core have been constructed by linking the two halves of corresponding Asp/Glu dendrons by 1,3 - bifunctional adamantane unit. Energy minimization and 1H NMR studies have shown these scaffoldings to adopt increasingly globular and compact architecture with each succeeding generation.

Dichlorophosphorylation of Adamantanols and 1-Adamantylcarbinols in Trifluoroacetic Acid

A convenient method for dichlorophosphorylation of adamantanols and 1-adamantyl alcohols with phosphorus trichloride in trifluoroacetic acid is described. The dichlorophosphoryl group is selectively introduced to the different positions of the adamantane nucleus as well as to the α-position of the side chain. The dichlorophosphorylation of 1-adamantylmethanol is found to be accompanied by adamantane-homoadamantane rearrangement leading to 3-homoadamantylphosphonic dichloride in 70% yield.

Synthesis and antiviral activity of sulfur-containing derivatives of adamantane

2 M e t h y t t h i o c a r b o n y l a m i n o a d a m a n t a n e ( V I I I ) was s y n t h e s i z e d by t h e r e a c t i o n o f 2 a d a m a n t o ] with a solution of methylthiocyanate in sulfuric acid, which excluded isomerization to a lsubstituted derivative, characteristic of adamantane compounds [8]. The PMR spectrum of thiocarbamate VIII contains a doublet of an ~-proton at 3.99 ppm (JH~HN 6 Hz), which confirms the bond of the nitrogen atom with the bridge carbon atom of the adamantane nucleus.

High-performance liquid chromatography of methyl esters of diamantane and adamantane car☐ylic acids

Chromatographic elution data for methyl and dimethyl esters of adamantane and diamantane derivatives of car☐ylic and dicar☐ylic acids have been determined using silica gel as the stationary phase. Eleven mobile phase containing n-heptane and/or diethyl ether, 2-proponal and chloroform were used in different concentration. Among all the compounds tested, esters having two functional groups have a longer retention time than esters having only one −COOCH 3 group. The influence of the position of −COOCH 3 groups on the chromatographic behaviur is discussed. For esters having the same formal substitution type, the elution time decreases with increasing size of the basic skeleton. The introduction of an alkyl group into the adamantane nucleus results in a decrease in the retention time of the relevant ester, while the introduction of an alkyl group between the adamantane skeleton and the −COOCH 3 group results in an increase in retention time. The effects of mobile phase composition on elution data for the compounds studied are discussed.

A study of deuterium exchange in adamantane carboxylic acids and alcohols under electron impact

AbstractThe mass spectra of 1‐adamantyl substituted carboxylic acids and alcohols with and without deuterated hydroxyl groups were studied. Deuterium exchange between functional group and adamantane nucleus was observed and a possible explantation of the phenomenon is given.

Study of alkyl adamantanes by NMR spectroscopy using 13C nuclei

1. 1. 13C NMR spectra of twelve alkyl adamantanes were studied and their structures correlated with carbon chemical displacement. It was shown that 13C NMR spectroscopy is a very effective method for investigating alkyl adamantane structures and at the same time enables the type of substitution in the adamantane nucleus to be determined. 2. 2. It was established that the effect of alkyl substituents on chemical displacements of 13C in di- and polyakyl adamantanes is additive. 3. 3. It was found that alkyl and adamantyl radicals have a mutual de-screening effect in the alkyl adamantane system showing a displacement to the weak field of peaks of the α-carbon atom of alkyl and nearest carbon atoms of adamantane nucleus. 4. 4. It was established for 2-alkyl adamantanes that γ-syn-carbon atoms of the adamantane nucleus interact with alkyl substituents: this is shown by the difference of chemical shifts of γ-syn- and γ-anti-carbon atoms of the adamantane nucleus.

Mass spectrometric study of alkyladamantanes

1. 1. Mass-spectra of 17 C 12C 16 alkyladamantanes containing substituents (methyl, ethyl, n-propyl and n-butyl) in different positions on the adamantane nucleus were investigated. 2. 2. The stability to electron impact of the molecular ion of mono-alkyl-adamantanes decreases with increased chain length of the substituents; with the same length of substituent, stability is higher for 2-mono-alkyladamantanes than for 1-mono-alkyladamantanes. 3. 3. For all the compounds studied the decomposition of the molecular ion results chiefly in the formation of an adamantyl ion with m.e. 135 (mono-alkyl-adamatanes) or its homologous (di-, tri- and tetra-alkyladamantanes).

Preparation of ring labelled adamantane derivatives II. 2‐adamantanone‐2−14C, adamantane‐2−14C and 1‐methyladamantane‐2 or 4−14C

AbstractA high‐yield, relatively simple synthetic route leading to incorporation of 14C into the secondary position of the adamantane nucleus is described. The synthesis was achieved by the sequence shown in Figure 2. The key steps involved the introduction of a 14C label by diazomethane‐14C ring expansion of adamantanone to give 4‐homoadamantanone‐4−14C (I). Benzylic acid rearrangement of the corresponding homoadamantane diketone (II) gave hydroxy acid (III) which was converted by a novel reaction (SOCl2/benzene) to 2‐adamantanone‐2−14C (IV). The overall yield of labelled 2‐adamantanone was 66%. Wolff‐Kishner reduction of (IV) gave adamantane‐2−14C (V). This was converted to the l‐methyl derivative (VII) by treatment of the corresponding bromide (VI) with methylmagnesium bromide.

Hydride transfer reactions of the adamantyl cation (IV): Synthesis of 1,4‐ and 2,6‐substituted adamantanes by oxidation with sulfuric acid

AbstractThe oxidation of adamantane by fuming sulfuric acid to 1,3‐, 1,4‐, and 2,6‐dihydroxyadamantane is discussed. The reactions are considered as hydride transfers from the adamantane nucleus to the acid. A synthetic procedure for 2,6‐adamantanedione and 5‐hydroxy‐2‐adamantanone is described.

Functionalization and cleavage of adamantane with lead tetra-acetate; the formation of 2(3 ? 4)abeo-adamantane from adamantane

Two different oxidative reactions of the adamantane nucleus with lead tetra-acetate are described. With adamantane and 2-adamantan-1-ylethanol in acetic acid sequential introduction of acetate groups at the bridgehead position occurs. In the presence of iodine, adamantan-1-ol affords tricyclo[4,3,1,03,8] decan-4-one via a bicyclo [3,3,1]-nonanone.