title: Stereocontrolled synthesis of syn-β-Hydroxy-α-amino acids by direct aldolization of pseudoephenamine glycinamide.
abstract: β-Hydroxy-α-amino acids figure prominently as chiral building blocks in chemical synthesis and serve as precursors to numerous important medicines. Reported herein is a method for the synthesis of β-hydroxy-α-amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one-flask protocol. Enolization of (R,R)- or (S,S)-pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of LiCl followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L- or D-threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55-98 %, and are readily transformed into β-hydroxy-α-amino acids by mild hydrolysis or into 2-amino-1,3-diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138 (USA).
authors.forename: Ian B
authors.initials: IB
authors.lastname: Seiple
authors.forename: Jaron A M
authors.initials: JA
authors.lastname: Mercer
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Sussman
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Myers
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis*; D000662:Amphetamines / Q000737:chemistry*; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D006868:Hydrolysis; D007659:Ketones / Q000737:chemistry; D018021:Lithium Chloride / Q000737:chemistry; D018020:Lithium Compounds / Q000737:chemistry; D015394:Molecular Structure; D012821:Silanes / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D000596:Amino Acids; D000662:Amphetamines; D007659:Ketones; D018020:Lithium Compounds; D012821:Silanes; C587965:pseudoephenamine; C018556:glycine amide; D018021:Lithium Chloride; C442341:lithium hexamethyldisilazide; D005998:Glycine
keywords: aldol reaction; amino acids; asymmetric synthesis; chiral auxiliaries; synthetic methods