The stereoselective synthesis of amino acids for biosynthetic studies.
Date
1997
Authors
Davis, Danny Thomas.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
This work provides a new general method for the synthesis of enantiomerically pure (R)-amino acids and possibly scD-threo-$\beta$-hydroxy-$\alpha$-amino acids. (R)- and (S)-Lysine and scD-threo-$\beta$(p-nitrophenyl)serine are required for future investigations of two metabolic pathways in our laboratory. For example, isotopically labelled (R)- and (S)-lysine are needed to examine the catabolism of this amino acid in Fusobacterium species, anaerobic bacteria associated with the gastrointestinal tract. Also, an investigation of the final steps in the biosynthesis of chloramphenicol, an antibiotic produced by cultures of Streptomyces venezuelae, requires the preparation of potential precursors from isotopically labelled scD-threo-$\beta$-(p-nitrophenyl)serine.
(S)-Amino acids were synthesized by the Belokon method (JCS Perkin I, 1988 and JACS 107, 1985), and the method was extended to include the preparation of (R)-amino acids in high yields and enantiomeric purity.
Alkylation of the (S)-BPB-complex with a series of cyanoalkylbromides led to a series of cyano (S)-amino acids after hydrolysis of the complex. The stereochemistry of the alkylation step was established by x-ray crystallography of an alkylated complex and by optical rotation measurements and hplc analysis of the isolated cyano amino acids. The corresponding series of cyano (R)-amino acids was made, demonstrating the first use of the (R)-BPB complex for the preparation of enantiomerically pure (R)-amino acids. The versatility of the synthetic approach was demonstrated by the preparation of the (R) and (S) series of acidic and basic amino acids including $\alpha$-aminoadipic acid and lysine.
Asymmetric routes to other non-protein amino acids, e.g., (2S,4R)- and (2S,4S-dihydroxynorvaline and all the steteoisomers of differentially protected 2,6-diaminopimelic acid are presented. Preliminary experiments suggest that the synthesis of scD-threo-$\beta$-hydroxy-$\alpha$-aminoacids can be achieved by condensation of the (R)-BPB-complex with an aldehyde.
Thesis (Ph.D.)--Dalhousie University (Canada), 1997.
(S)-Amino acids were synthesized by the Belokon method (JCS Perkin I, 1988 and JACS 107, 1985), and the method was extended to include the preparation of (R)-amino acids in high yields and enantiomeric purity.
Alkylation of the (S)-BPB-complex with a series of cyanoalkylbromides led to a series of cyano (S)-amino acids after hydrolysis of the complex. The stereochemistry of the alkylation step was established by x-ray crystallography of an alkylated complex and by optical rotation measurements and hplc analysis of the isolated cyano amino acids. The corresponding series of cyano (R)-amino acids was made, demonstrating the first use of the (R)-BPB complex for the preparation of enantiomerically pure (R)-amino acids. The versatility of the synthetic approach was demonstrated by the preparation of the (R) and (S) series of acidic and basic amino acids including $\alpha$-aminoadipic acid and lysine.
Asymmetric routes to other non-protein amino acids, e.g., (2S,4R)- and (2S,4S-dihydroxynorvaline and all the steteoisomers of differentially protected 2,6-diaminopimelic acid are presented. Preliminary experiments suggest that the synthesis of scD-threo-$\beta$-hydroxy-$\alpha$-aminoacids can be achieved by condensation of the (R)-BPB-complex with an aldehyde.
Thesis (Ph.D.)--Dalhousie University (Canada), 1997.
Keywords
Chemistry, Organic.