Simple, Highly Enantioselective Access to Quaternary 1,3,4,4‐Tetrasubstituted β‐Lactams from Amino Acids: A Solid‐Phase Approach

• Published in: Advanced synthesis & catalysis Vol. 350; no. 14‐15; pp. 2279 - 2285
• Main Authors: Pérez‐Faginas, Paula, Aranda, M. Teresa, Coady, Laoise, García‐López, M. Teresa, González‐Muñiz, Rosario
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 06.10.2008; Wiley
• Subjects: amino acids; asymmetric synthesis; Chemistry; Chemistry, Applied; Chemistry, Organic; cis‐β‐lactams; peptidomimetics; phosphazenes; Physical Sciences; Science & Technology; solid‐phase synthesis; cis-beta-lactams; ASYMMETRIC-SYNTHESIS; STAUDINGER REACTION; BUILDING-BLOCKS; amino acids; HUMAN CYTOMEGALOVIRUS PROTEASE; phosphazenes; solid-phase synthesis; CHOLESTEROL ABSORPTION; asymmetric synthesis; COMBINATORIAL SYNTHESIS; RECENT PROGRESS; peptidomimetics; C-ALPHA-CYCLIZATION; STEREOSELECTIVE-SYNTHESIS; INHIBITORS
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.200800432

An operationally simple four‐step procedure for the solid‐phase synthesis of chiral (3S,4S)‐1,3,4,4‐tetrasubstituted β‐lactams is described. The key step for the four‐membered ring formation consisted in the enantioselective phosphazene base‐assisted cyclization of resin‐bound N‐(alkyl)‐N‐[(S)‐2‐chloropropionyl]amino acid derivatives. A low‐epimerization process during the incorporation of the 2S‐chloropropionyl moiety into the N‐alkylamino acid resins was crucial for the final stereochemical outcome, since the 3,4‐stereochemistry was exclusively dictated by the configuration of this moiety. To evaluate the scope of this procedure a small library of quaternary, highly functionalized β‐lactams has been generated.