Amino acids of the adamantane series. I. Synthesis and antiviral activity of α-amino acids of the adamantane series and their derivatives

Conformationally rigid cyclic α-amino acids in the design of peptidomimetics, peptide models and biologically active compounds

“…Three unsubstituted amino acids with the adamantane cage are known to date, viz., 2-aminoadamantane-2-carboxylic acid (172), 252,253 (1-adamantyl)glycine (173) 254 and 3-(1-adamantyl)alanine ( 174) 255 (the latter can be classified as CRA only formally; such a remote w 3 -rigidity plays only a minor role) and 1,3adamantylidenediglycine (175). 256 Derivatives of the acids 172 ± 174 methylated at bridgehead carbon atoms have also been prepared.…”

“…252,253 Compounds 173 and 174 have been prepared starting from adamantylacetic and adamantylpropionic acids, respectively, by a-halogenation (e.g., according to the Hell ± Volhard ± Zelinsky reaction) followed by substitution of the amino group for the halogen atom. 255 Compound 175 has been prepared similarly. 256 In the case of cubane, only one CRA 176 is known, which is a glutamic acid analogue.…”

“…255 Compound 175 has been prepared similarly. 256 In the case of cubane, only one CRA 176 is known, which is a glutamic acid analogue. 257 Its synthesis has been performed starting from dimethylcubanedicarboxylate using a method similar to that used for the preparation of bicyclo[1.1.1]pentane (166) considered above.…”

“…Compounds 173 ± 175 manifest antiviral activity, which is, however, solely due to the presence of the adamantyl substituent. 255 A study of binding of compound 176 to metabotropic glutamate receptors has revealed that it represents a selective antagonist of mGluR1. 257 The consideration of polycyclic amino acids with an exocyclic nitrogen atom will be incomplete, if we omit another unique substance, viz., pentacyclic CRA 177, which is a pentacyclo[5.4.0.0 2,6 .0 3,10 .0 5,9 ]undecane derivative.…”