Enantioselective Synthesis of α-Quaternary Amino Acid Derivatives by Sequential Enzymatic Desymmetrization and Curtius Rearrangement of α,α-Disubstituted Malonate Diesters
Violeta Iosub
Anton R. Haberl
Jennifer Leung
Michael Tang
Kannan Vembaiyan
Masood Parvez
Thomas G. Back
10.1021/jo902584r.s001
https://acs.figshare.com/articles/journal_contribution/Enantioselective_Synthesis_of_Quaternary_Amino_Acid_Derivatives_by_Sequential_Enzymatic_Desymmetrization_and_Curtius_Rearrangement_of_Disubstituted_Malonate_Diesters/2786524
A convenient and versatile enantioselective synthesis of biologically important α-quaternary amino acid derivatives was based on the sequential double alkylation or arylation of dimethyl malonate, followed by desymmetrization with porcine liver esterase (PLE) and Curtius rearrangement. The PLE-mediated hydrolysis of the prochiral dialkylated malonate diesters produced the corresponding chiral half-esters in high yield and with enantiomeric excesses of 43% to >98%. Curtius rearrangement of the latter products, after trapping of the intermediate isocyanates with benzyl alcohol or amines, afforded the corresponding Cbz-protected amino esters or ureas. The absolute configurations of the major products in five examples were established by conversion to compounds with known specific rotations, or by X-ray crystallography of derivatives obtained with chiral amines of known configuration.
2010-03-05 00:00:00
porcine liver esterase
enantiomeric excesses
configuration
dimethyl malonate
enantioselective synthesis
acid derivatives
Curtius Rearrangement
Curtius rearrangement
prochiral dialkylated malonate diesters
benzyl alcohol
PLE
chiral amines
latter products
Enantioselective Synthesis