title: New synthetic technology for efficient construction of alpha-hydroxy-beta-amino amides via the Passerini reaction.
abstract: [reaction: see text] The Passerini reaction of N-protected amino aldehydes, isonitriles, and TFA using pyridine-type bases proceeds under mild conditions and directly affords alpha-hydroxy-beta-amino amide derivatives in moderate to high yields. These adducts are readily hydrolyzed to alpha-hydroxy-beta-amino carboxylic acids. Application of these key intermediates to concise syntheses of P(1)-alpha-ketoamide protease inhibitors is illustrated.
authors.affiliation: Department of Medicinal Chemistry, Corvas International, Inc., 3030 Science Park Road, San Diego, California 92121, USA. ed_semple@corvas.com
authors.forename: J E
authors.initials: JE
authors.lastname: Semple
authors.forename: T D
authors.initials: TD
authors.lastname: Owens
authors.forename: K
authors.initials: K
authors.lastname: Nguyen
authors.forename: O E
authors.initials: OE
authors.lastname: Levy
mesh_terms: D000577:Amides / Q000138:chemical synthesis*; D000596:Amino Acids / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry; D007651:Keto Acids / Q000138:chemical synthesis; D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D011480:Protease Inhibitors / Q000138:chemical synthesis; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000596:Amino Acids; D005449:Fluorenes; D007651:Keto Acids; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D011480:Protease Inhibitors; D007930:Leucine; C012211:ubenimex