Enantioselective Au(I)-catalyzed dearomatization of 1-naphthols with allenamides through Tethered Counterion-Directed Catalysis.

The Tethered Counterion-Directed Catalysis (TCDC) approach has been applied to the enantioselective Au(I) catalyzed dearomatizations of 1-naphthols with allenamides. Stereocontrol is ensured by the intramolecular ion-pairing between the chiral gold-tethered phosphate and an iminium unit, that provides a rigid, well-defined chiral environment to the key electrophilic intermediate.

From acyclic to cyclic α-amino vinylphosphonates by using ring-closing metathesis.

Acyclic α-amino vinylphosphonates were alkylated through the Mitsunobu reaction then diolefinic compounds hence formed were subjected to RCM. Studies on the scope and limitations of RCM with these sterically hindered α-amino vinylphosphonates are detailed.

Cerium(IV) ammonium nitrate mediated 5-endo-dig cyclization of α-amino allenylphosphonates to spirodienones.

α-Amino allenylphosphonates were treated with cerium(iv) ammonium nitrate under various conditions to form spirodienones in good to excellent yields. The 5-endo-dig cyclization proceeds through the formation of a key iminium intermediate. A comprehensive study on the nature of the solvent used for this reaction was undertaken resulting in the formation of three types of spirodienone scaffolds.

[2,3]-Sigmatropic rearrangement of ynamides: preparation of α-amino allenephosphonates.

α-Amino allenephosphonates were easily prepared in two steps from protected amines, propargyl alcohols, and chlorophosphites. First, ynamides were synthesized from unprotected 1-bromopropargyl alcohols using a copper(II) catalyzed coupling reaction. In the second step, the previously prepared ynamides were transformed directly to allenes through a [2,3]-sigmatropic rearrangement of propargyl phosphites. This efficient method led to the formation of a series of α-amino allenephosphonates with diverse substituents on the amine, the phosphonate, and the allene moieties.

Total synthesis of the interleukin-1beta converting enzyme inhibitor EI-1941-2 using tandem oxa-electrocyclization/oxidation1.

[reaction: see text] The total synthesis of the interleukin-1beta converting enzyme inhibitor EI-1941-2 was achieved utilizing tandem oxidation/oxa-electrocyclization/oxidation to access a key alpha-pyrone intermediate. Support for the tandem reaction mechanism was obtained by evaluation of a stepwise oxidation protocol.

Azetidinic amino acids: stereocontrolled synthesis and pharmacological characterization as ligands for glutamate receptors and transporters.

A set of ten azetidinic amino acids, that can be envisioned as C-4 alkyl substituted analogues of trans-2-carboxyazetidine-3-acetic acid (t-CAA) and/or conformationally constrained analogues of (R)- or (S)-glutamic acid (Glu) have been synthesized in a diastereo- and enantiomerically pure form from beta-amino alcohols through a straightforward five step sequence. The key step of this synthesis is an original anionic 4-exo-tet ring closure that forms the azetidine ring upon an intramolecular Michael addition. This reaction was proven to be reversible and to lead to a thermodynamic distribution of two diastereoisomers that were easily separated and converted in two steps into azetidinic amino acids. Azetidines 35-44 were characterized in binding studies on native ionotropic Glu receptors and in functional assays at cloned metabotropic receptors mGluR1, 2 and 4, representing group I, II and III mGlu receptors, respectively. Furthermore, azetidine analogues 35, 36, and 40 were also characterized as potential ligands at the glutamate transporter subtypes EAAT1-3 in the FLIPR Membrane Potential (FMP) assay. The (2R)-azetidines 35, 37, 39, 41 and 43 were inactive in iGlu, mGlu and EAAT assays, whereas a marked change in the pharmacological profile at the iGlu receptors was observed when a methyl group was introduced in the C-4 position, compound 36 versus t-CAA. At EAAT1-3, compound 35 was inactive, whereas azetidines 36 and 40 were both identified as inhibitors and showed selectivity for the EAAT2 subtype.