152673-15-9Relevant academic research and scientific papers
Stereocontrolled synthesis of 3-substituted azetidinic amino acids
Sivaprakasam, Mangaleswaran,Couty, Fran?ois,Evano, Gwilherm,Srinivas,Sridhar,Rao, K. Rama
, p. 781 - 785 (2007/10/03)
A set of enantiomerically pure N-disubstituted β-amino alcohols was chlorinated by treatment with thionyl chloride. This reaction gave a mixture of regioisomeric chlorides that could be equilibrated to the more stable regioisomer by heating in DMF. The chlorides thus obtained were engaged in an intramolecular anionic ring-closure and gave access to fully protected enantio- and diastereomerically pure 2,3-cis-disubstituted azetidinic amino acids. One of the latter was deprotected and included in a short peptide sequence. Georg Thieme Verlag Stuttgart.
Azetidinic amino acids: Stereocontrolled synthesis and pharmacological characterization as ligands for glutamate receptors and transporters
Braeuner-Osborne, Hans,Bunch, Lennart,Chopin, Nathalie,Couty, Francois,Evano, Gwilherm,Jensen, Anders A.,Kusk, Mie,Nielsen, Birgitte,Rabasso, Nicolas
, p. 3926 - 3936 (2007/10/03)
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 ss-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. The Royal Society of Chemistry 2005.
Asymmetric synthesis of functionalized azetidines through intramolecular Michael additions
Carlin-Sinclair, Abel,Couty, Fran?ois,Rabasso, Nicolas
, p. 726 - 728 (2007/10/03)
Enantiopure 2-cyano azetidines were prepared in good yields from β-amino alcohols. This synthesis is based on two important steps: (i) Wittig olefination of a transient amino aldehyde derived from a N-cyanomethylated β-amino alcohol and (ii) a 4-exotet ring closure through the intramolecular Michael addition of a lithiated α-amino nitrile. The former step is stereoselective. The thus produced functionalized azetidines were transformed into conformationnally constrained analogues of glutamic acid.
A practical stereoselective synthesis of (2S, 4S)-4-tert-butoxycarbonylamino-2-methylpyrrolidine
Qun, Li,Chu, Daniel T. W.,Raye, Kathleen,Claiborne, Akiyo,Seif, Louis,Macri, Bryan,Plattner, Jacob J.
, p. 8391 - 8394 (2007/10/02)
Two practical syntheses of (2S, 4S)-4-tert-butoxycarbonylamino-2-methylpyrrolidine, an important intermediate for quinolone antibacterial agents, have been developed through the combination of diastereo and enantioselective reactions starting from ethyl crotonate and L-alanine, respectively.
