A combination of an achiral pyridoxal analogue and a chiral base has been developed for catalytic deuteration of L-alanine with inversion of stereochemistry to give deuterated D-alanine under mild conditions (neutral pD and 25 °C) without the use of any protecting groups. This system can also be used for catalytic deuteration of D-alanine with retention of stereochemistry to give deuterated D-alanine. Thus a racemic mixture of alanine can be catalytically deuterated to give an enantiomeric excess of deuterated D-alanine. While catalytic deracemization of alanine is forbidden by the second law of thermodynamics, this system can be used for catalytic deracemization of alanine with deuteration. Such green and biomimetic approach to catalytic stereocontrol provides insights into efficient amino acid transformations.
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http://dx.doi.org/10.1002/anie.201503616 | DOI Listing |
J Med Chem
August 2024
Department of Chemistry, Stony Brook University, John S. Toll Drive, Stony Brook, New York 11794-3400, United States.
d-Amino acids such as d-alanine are substrates for bacterial peptidoglycan biosynthesis and are selectively taken up by bacteria and not mammalian cells. Consequently, d-amino acid metabolism is an attractive target for antibiotic discovery and the development of bacteria-specific imaging agents. d-Fluoroalanine and the deuterium-labeled analogue fludalanine (MK641) were originally explored as antibiotics by Merck but failed in clinical trials due to unaccepted toxicity.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
August 2015
Department of Chemistry, University of Toronto, 80 St George Street, Toronto, ON, M5S 3H6 (Canada) http://www.diaminopharm.com.
A combination of an achiral pyridoxal analogue and a chiral base has been developed for catalytic deuteration of L-alanine with inversion of stereochemistry to give deuterated D-alanine under mild conditions (neutral pD and 25 °C) without the use of any protecting groups. This system can also be used for catalytic deuteration of D-alanine with retention of stereochemistry to give deuterated D-alanine. Thus a racemic mixture of alanine can be catalytically deuterated to give an enantiomeric excess of deuterated D-alanine.
View Article and Find Full Text PDFJ Am Chem Soc
February 2013
Department of Chemistry, University of California-Davis, One Shields Avenue, Davis, California 95616, USA.
The catalytic effects of perdeuterating the pyridoxal phosphate-dependent enzyme alanine racemase from Geobacillus stearothermophilus are reported. The mass of the heavy perdeuterated form is ~5.5% greater than that of the protiated form, causing kinetic isotope effects (KIEs) of ~1.
View Article and Find Full Text PDFEur J Mass Spectrom (Chichester)
April 2013
Department of Chemistry, University of Warwick, Coventry, UK.
A novel nano-electrospray emitter has been developed containing two separated channels running throughout the length of the emitter. The emitters have been fabricated from "theta-shaped" borosilicate capillaries. Loading of different solutions into the two different channels opens up the possibility to study short timescale interactions within a Taylor cone common to both channels.
View Article and Find Full Text PDFJ Am Chem Soc
September 2007
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA.
The pyridoxal phosphate dependent alanine racemase catalyzes the interconversion of L- and D-alanine. The latter is an essential component of peptidoglycan in cell walls of Gram-negative and -positive bacteria, making alanine racemase an attractive target for antibacterials. Global analysis of protiated and deuterated progress curves simultaneously enables determination of intrinsic kinetic and equilibrium isotope effects for alanine racemase.
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