title: A straightforward route to enantiopure 2-substituted-3,4-dehydro-β-proline via ring closing metathesis.
abstract: The synthesis of unusual cyclic amino acids, that may be envisaged as proline analogs, is an area of great interest for their potential applications as scaffolds for the design of bioactive peptidomimetics or units for the creation of novel foldamers. We have carried out the preparation of cyclic dehydro-β-amino acids starting from allylic carbonates via a two-step allylic amination/ring closing metathesis (RCM) protocol. The introduction of the allylamino moiety has been carried out either without a catalyst, through an S(N)2' reaction, or in the presence of iridium complexes. The backbone of the allylamino intermediates contains two unsaturations, thus suggesting that RCM could be a valuable tool for the preparation of dihydropyrrole scaffolds. A similar reaction has been already reported in the literature for racemic aromatic-substituted substrates, but no examples of enantiopure derivatives bearing aliphatic chains have been reported. The reaction was optimized by testing different Grubbs' catalysts and carbamate nitrogen protecting groups. Moreover, in view of a future application of these dehydro-β-amino acids as central core of peptidomimetics, the malonate chain was also used to protect nitrogen prior to RCM.
authors.affiliation: Department of Chemistry, G. Ciamician, University of Bologna, Via Selmi 2, 40126, Bologna, Italy. alessandra.tolomelli@unibo.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tolomelli
authors.forename: Luca
authors.initials: L
authors.lastname: Gentilucci
authors.forename: Elisa
authors.initials: E
authors.lastname: Mosconi
authors.forename: Angelo
authors.initials: A
authors.lastname: Viola
authors.forename: Enrico
authors.initials: E
authors.lastname: Paradisi
mesh_terms: D000586:Amination; D000598:Amino Acids, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002254:Carbonates / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D007495:Iridium; D057786:Peptidomimetics; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000598:Amino Acids, Cyclic; D002254:Carbonates; D004952:Esters; D057786:Peptidomimetics; D011758:Pyrroles; D007495:Iridium; D011392:Proline; C072401:beta-proline