Synthesis of conformationally constrained tricyclic beta-lactam enantiomers through Ugi four-center three-component reactions of a monoterpene-based beta-amino acid.
(1R,2R,3S,4R)-2-Amino-6,6-dimethylbicyclo[3.1.1]heptane-3-carboxylic acid 1 was reacted with three aldehydes and two isocyanides in methanol, in water, and under solvent-free conditions to prepare enantiomeric beta-lactams via U-4C-3CRs. The yields in methanol were found to be from acceptable to good. High diastereoselectivities of the reactions were observed, and the diastereoisomers were successfully separated in most cases. In water or under solvent-free conditions, the yields were similar to those in methanol when the aldehyde was pivalaldehyde or propionaldehyde. The advantages of water are the facile isolation of the precipitated product and the shorter reaction time.
Szakonyi
Zsolt
Z
Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, 6720, Szeged, Hungary.
Sillanpää
Reijo
R
Fülöp
Ferenc
F
D000596:Amino Acids / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D000432:Methanol / Q000737:chemistry; D039821:Monoterpenes / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry
D000596:Amino Acids; D039821:Monoterpenes; D047090:beta-Lactams; D014867:Water; D000432:Methanol