ABSTRACT
An expedient, five step synthesis of caprolactam 1 is reported starting from natural L-homoserine. The key step is a chemoselective reductive cyclization of alpha,beta-unsaturated nitrile 10 mediated by Raney-Co type metals. This hydrogenation is extensively investigated in order to account for the observed product distribution and yields.
Subject(s)
Cobalt/chemistry , Nitriles/chemistry , Aldehydes/chemical synthesis , Aldehydes/chemistry , Caprolactam/chemistry , Cyclization , Homoserine/chemical synthesis , Homoserine/chemistry , Isomerism , Methionine/chemistry , Molecular Structure , Oxidation-Reduction , TemperatureABSTRACT
A direct asymmetric hydrogenation of unprotected enamino esters and amides is described. Catalyzed by Rh complexes with Josiphos-type chiral ligands, this method gives beta-amino esters and amides in high yield and high ee (93-97% ee). No acyl protection/deprotection is required.
Subject(s)
Amides/chemical synthesis , Amines/chemistry , Amino Acids/chemistry , Esters/chemical synthesis , Alkenes/chemistry , Catalysis , Hydrogenation , StereoisomerismABSTRACT
Pure (Z)-enamines readily prepared from beta-ketoesters and amides using (S)-phenylglycine amide were hydrogenated with very high diastereoselectivities (up to 200:1) using heterogeneous catalysis. Hydrogenolytic cleavage of the (S)-phenylglycine amide afforded the corresponding chiral beta-aminoesters and amides. The high geometrical purity of the (Z)-enamine and a simple activation procedure for the PtO2 catalyst are essential in achieving high selectivity.
Subject(s)
Amines/chemistry , Amino Acids/chemistry , Amides/chemical synthesis , Amides/chemistry , Amino Acids/chemical synthesis , Catalysis , Crystallography, X-Ray , Deuterium , Esters/chemical synthesis , Esters/chemistry , Hydrogenation , StereoisomerismABSTRACT
The Thermotoga maritima aldolase gene has been cloned into a T7 expression vector and overexpressed in Escherichia coli. The preparation yields 470 UL(-1) of enzyme at a specific activity of 9.4 U mg(-1). During retroaldol cleavage of KDPG, the enzyme shows a k(cat) that decreases with decreasing temperature. A more than offsetting decrease in K(m) yields an enzyme that is more efficient at 40 degrees C than at 70 degrees C. The substrate specificity of the enzyme was evaluated in the synthetic direction with a range of aldehyde substrates. Although the protein shows considerable structural homology to KDPG aldolases from mesophilic sources, significant differences in substrate specificity exist. A preparative scale reaction between 2-pyridine carboxaldehyde and pyruvate provided product of the same absolute configuration as mesophilic enzymes, but with diminished stereoselectivity.
