title: Efficient and regiospecific syntheses of peptides with piperazic and dehydropiperazic acids via a multicomponent reaction.
abstract: Peptides containing N2-acyl piperazic or 1,6-dehydropiperazic acids can be formed efficiently via a novel multicomponent reaction of 1,4,5,6-tetrahydropyridazines, isocyanides, and carboxylic acids. Remarkably, the reaction's induced intramolecularity can enable the regiospecific formation of products with N2-acyl piperazic acid, which counters the intrinsic and troublesome propensity for piperazic acids to react at N1 in acylations. The utility of the methodology is demonstrated in the synthesis of the bicyclic core of the interleukin-1β converting enzyme inhibitor, Pralnacasan.
authors.affiliation: Department of Chemistry, Brown University , 324 Brook Street, Providence, Rhode Island 02912, United States.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Handy
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Totaro
authors.forename: Charlie P
authors.initials: CP
authors.lastname: Lin
authors.forename: Jason K
authors.initials: JK
authors.lastname: Sello
mesh_terms: D000215:Acylation; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry; D020170:Caspase 1 / Q000187:drug effects; D061945:Caspase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D001381:Azepines; D001688:Biological Products; D002264:Carboxylic Acids; D061945:Caspase Inhibitors; D007546:Isoquinolines; D009570:Nitriles; D010455:Peptides; D011724:Pyridazines; C014756:piperazic acid; D020170:Caspase 1; C476331:pralnacasan