Assisted hydrolysis of the nitrile group of 2-aminoadamantane-2-carbonitrile

Abstract

Attempts to hydrolyse the nitrile group of 2-aminoadamantane-2-carbonitrile by mineral acid or alkali have been unsuccessful. However, treatment of the aminonitrile with benzaldehyde in alkaline solution gives the benzal derivative of the α-aminoamide, readily hydrolysed to the α-aminoamide. Alternatively, benzoylation of the amino group followed by acid hydrolysis gives successively the α-benzamido acid and the α-amino acid. Possible mechanisms for these facilitated hydrolyses are advanced.

En route towards the peptide γ‐helix: X‐ray diffraction analyses and conformational energy calculations of Adm‐rich short peptides

“…Following the procedure reported by Baxendale et al , we synthesized the free, rigid, highly lipophilic, tricyclic Adm α ‐amino acid hydrochloride via a variant of the classical Strecker synthesis. The hydrolytic step of its last intermediate, 2‐benzamidoadamantane‐2‐carboxylic acid, proceeds under relatively mild acidic conditions, affording the desired compound free from the impurities characteristic of the Bucherer–Bergs strategy.…”

“…The last step of this latter reaction (basic hydrolysis of the hydantoin intermediate) requires very severe experimental conditions resulting in the production of a significant amount of inorganic impurities. In our procedure, we identified the following synthetic intermediates, all of them described in the literature except the first: 2‐hydroxyadamantane‐2‐carbonitrile (cyanohydrin), 2‐aminoadamantane‐2‐carbonitrile , 2‐benzamidoadamantane‐2‐carbonitrile , and 2‐benzamidoadamantane‐2‐carboxylic acid . In our 3D–structure of the crystalline Adm cyanohydrin, solved by X‐ray crystallography, two independent molecules characterize the asymmetric unit (Figure ).…”

“…Among the variety of building blocks suggested as efficient γ-turn inducers or mimics (see, for example, refs. [11,[30][31][32][33][34][35]), which might be useful for the construction of γ-helices, we selected the C α -tetrasubstituted, achiral 2-aminoadamantane-2-carboxylic acid (Adm; Figure 2) because of the following: (i) its preparation from the commercially available 2-adamantone [36][37][38][39][40] and (ii) an initial solution investigation by NMR and IR absorption [35] on one derivative, Ac-Adm-NHMe (Ac, acetyl; NHMe, methylamino) and one very short peptide, the terminally blocked dipeptide Ac-Adm-Gly-NHMe, were already reported. In the latter publication, this α-amino acid was proposed as a 'promising γ-turn inducer for synthetic peptides'.…”

Photodecarboxylation of Adamantane Amino Acids Activated by Phthalimide

“…Phthalimide derivatives 3-6 were prepared in moderate to good yields by a condensation reaction between the corresponding amino acid and phthalic anhydride and using a modification [46] of a published procedure. [52,53] α-Amino acid 7, [54] which was synthesized according to a known procedure [55] by starting from 2-adamantanone through a hydantoin derivative, [54] was transformed into the corresponding phthalimide 3 in moderate yield (Scheme 2).…”

“…

Adamantane α-, -, and δ-amino acids activated by phthalimide (i.e., 3-6) were synthesized, and their photochemical reactivities were investigated. [52,53] α-Amino acid 7, [54] which was synthesized according to a known procedure [55] by starting from 2-adamantanone through a hydantoin derivative, [54] was transformed into the corresponding phthalimide 3 in moderate yield (Scheme 2).The syntheses of the adamantane -amino acids activated by phthalimide (i.e., 4 and 5) are shown in Scheme 3. The decarboxylations of the -amino acid derivatives were succeeded by cyclization reactions that afforded complex polycyclic molecules with potential biological interest.

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