Amines and amides of the adamantane series exhibit a broad spectrum of pharmacological activity, including analgesic [1], antiinflammatory [2], anticonvulsive [3], and antivirat [4, 5]. Adamantane and its derivatives are capable of changing the hexagonal packing of methylene groups in the alkyl chains of phospholipids, thus affecting the functional properties of membrane proteins. Data obtained on models of erythrocytic membranes and liposomes showed that remantadine may incorporate into the lipid membranes, modifying their structure and imparting to them a more "liquid-phase" character [6]. In the context of an investigation of the membrane activity of adamantane derivatives and the role of this factor in the antiviral and cytotoxic properties of these compounds, of special interest are amides containing, on the one hand, the adamantyl radical and, on the other hand, an amino acid residue.The purpose of this work was to synthesize some new adamantane-containing amino acids (IIIa, IIIb, and IV) and to study their effects upon the state of hemoglobin and membranes in human blood erythrocytes.The adamantane-containing amino acids IIIa, IIIb, and IV were synthesized by interaction of l-adamantanecarboxylic (I) and (1-adamantyl)acetic (11) acids with glycine, D,L-alanine, and L-valine.Ilia. IIIb;, 1V Ad = l-adamantyl; n = 0 (I, Ilia, Illb), 1 (II, IV); R = H (Ilia), iso-Pr (lllb), Me (IV).
EXPERIMENTAL CHEMICAL PARTThe IR absorption spectra were measured on an IKS-29 spectrophotometer (LOMO, Russia) using samples pelletized i Samara State University, Samara, Russia. 2 State Technical University, Samara, Russia. 132 with KBr. The I H NMR spectra were recorded on a Bruker HX-90 spectrometer using CD3OD as the solvent and HMDS as the internal standard. The TLC analyses were conducted on Silufol UV-254 plates. The data of elemental analyses agree with the results of analytical calculations. (Ilia). To a solution of 2.25 g (30 mmole) of glycine in 7.5 ml of water were successively added 7.5 ml (30 mmole) of a 4 N aqueous NaOH solution, 7 ml of 1,4-dioxane, and eventually, by portions with stirring, a solution of 6 g (30 mmole) of adamantanoyl chloride in 20 ml of absolute 1,4-dioxane. As the reaction proceeded, 4 N aqueous NaOH solution was added to maintain the initial level of pH 9-11. The chloroanhydride solution was added in five portions over a time period of approximately 45 rain. The stirring was continued for 30 min at 20~ Then the reaction mixture was doubly diluted with water and acidified to pH 2-3 with HCI. The white clotted precipitate was filtrated, washed with water until neutral pH, dried, and recrystallized from acetone to obtain 6.4 g (90.0 %) of compound Illa; m.p.,[191][192] Aides Ilia and IV were obtained by similar procedures.
N-Adamantanoylglyeine