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The octadecaneuropeptide (ODN; QATVGDVNTDRPG LLDLK) and its C-terminal octapeptide (OP; RPGLLDLK), which exert anxiogenic activity, have been previously shown to increase intracellular calcium concentration ([Ca 21 ] i ) in cultured rat astrocytes through activation of a metabotropic receptor positively coupled to phospholipase C. It has also been found that the [7].The mechanism of action of endozepines is not fully understood. It has been initially proposed that these peptides act as inverse agonists of central-type benzodiazepine receptors [6] thus inhibiting the activity of the GABA Achloride channel complex [8]. Subsequently, endozepines were found to interact with peripheral-type BZ receptors and to stimulate cholesterol transport into mitochondria [9]. More recently, it has been shown that, in rat astrocytes, ODN activates a metabotropic receptor positively coupled to phospholipase C, leading to an increase in cytosolic calcium concentration [10,11]. Structure-activity relationship studies have shown that the C-terminal octapeptide of ODN (OP; ODN 11218 ) is the minimum sequence retaining full calcium-mobilizing activity [12]. The Ala-scan of OP has revealed that replacement of the Leu6 residue suppresses the activity of the peptide. It has also been found that the

The complexes between methyllithium and chiral 3-aminopyrrolidine (3-AP) lithium amides bearing a second asymmetric center on their lateral amino group were studied using multinuclear ((1)H, (6)Li, (13)C, (15)N) low-temperature NMR spectroscopies in tetrahydrofuran-d(8). The results indicate that lithium chelation forces the pyrrolidine ring of the 3-AP to adopt a norbornyl-like conformation and that robust 1:1 noncovalent complexes between methyllithium and 3-AP lithium amides form in the medium. A set of (1)H-(1)H and (1)H-(6)Li NMR cross-coupling correlations shows that the binding of methyllithium can take place along the "exo" or the "endo" face of this puckered structure, depending on the relative configuration of the lateral chiral group. This aggregation step renders the nitrogen of the 3-amino group chiral, the "exo" and "endo" topologies corresponding to the (S) and (R) configurations, respectively, of this atom. Density functional theory calculations show that the "exo" and "endo" arrangements are, for both diastereomers, almost isoenergetic even when solvent is taken into account. This result suggests that the formation of the mixed aggregates is under strict kinetic control. A relationship between the topology of these complexes and the sense of induction in the enantioselective alkylation of aromatic aldehydes by alkyllithiums is proposed.