290836-39-4Relevant academic research and scientific papers
Enantioselective synthesis of a-quaternary amino acid derivatives by sequential enzymatic desymmetrization and curtius rearrangement of α,α-disubstituted malonate diesters
Iosub, Violeta,Haberl, Anton R.,Leung, Jennifer,Tang, Michael,Vembaiyan, Kannan,Parvez, Masood,Back, Thomas G.
experimental part, p. 1612 - 1619 (2010/04/29)
(Figure Presented) A convenient and versatile enantioselective synthesis of biologically important α-quatemary 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.
