Spiro[2.2]pentane as a Dissymmetric Scaffold for Conformationally Constrained Analogues of Glutamic Acid:  Focus on Racemic 1-Aminospiro[2.2]pentyl-1,4-dicarboxylic Acids

Abstract

In search for novel conformationally constrained analogues of L-glutamic acid, a diastereodivergent synthesis of the four 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acid racemic pairs is reported along with their stereochemical assignment, conformational analysis, and preliminary biological evaluation as potential glutamate (ionotropic and metabotropic) ligands.

Non‐empirical calculations of NMR indirect carbon–carbon coupling constants. Part 7—Spiroalkanes

“…66 Earlier, molecular mechanics calculations of the steric strain in the conformers of monosubstituted spiro [5.5]undecanes were performed by Zefirov and co-workers. 67 Also, the anisochromism of spiro [5.5]undecane in 13 C NMR and the existence of four anisometric chair-chair conformers of 1-monosubstituted were investigated 24 and critically reinvestigated. 68 Enthalpies of combustion, formation and vaporization of spiro [5.5]undecane were measured by precision oxygen-bomb combustion calorimetry.…”

“…The presence of the spiro fragments in these compounds possessing specific geometries and unusual bonding environments 8,9 makes spiroalkanes especially attractive for theoretical studies in terms of their 13 C- 13 C transmission mechanisms involving and/or across spiro carbons. The most interesting and the most unusual member of this family is spiropentane (1), the ancestor of the spiroalkanes series, which will receive special attention further in this paper.…”

“…12 used as a dissymmetric scaffold for conformationally constrained analogues of glutamic acid. 13 Spiropentaneacetic acid showed in vivo inhibitory activity in rats and acted as a specific inhibitor of fatty acid oxidation without affecting amino acid metabolism.…”

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

“…Modifications to this molecule resulted in the identification of the analogues MGS0008 ( 3 ) [11] and MGS0028 ( 4 ) [12–13]. In addition, the conformationally constrained analogues of L-Glu 6a,b , 7 , 8 and 9a,b were reported [14–18] as either ionotropic or metabotropic glutamate receptors ligands, obtained by “freezing” the glutamate skeleton in search for subtype selective bioactive conformations [19].…”

Synthesis methods of (1-aminocyclopropyl)phosphonic acids

“…Yet the structural features of the molecule of the (1-aminocyclopropyl)phosphonic acid make it very promising for designing biologically active compounds [6][7][8]. These are, fi rstly, the presence of a tetrahedral phosphonate group resembling the transition state of the carboxy group providing the α-aminophosphonic acids with the properties of inhibitors of the enzymes of α-amino acids metabolism; secondly, the capability to form peptide bonds and to be built in the peptide chains; thirdly, the presence of a rigid three-membered ring considerably reducing the conformational mobility of the molecule (also that of the polypeptide) in whose structure it is included; this limitation is one of the widest applied approaches of the modern medical chemistry [8][9][10][11][12].…”