402828-03-9

Upstream product

• 402828-04-0 (S)-1-butyryloxymethyl-4-(p-tolyl)-2-azetidinone 
• 21161-19-3 (+/-)-4-(p-tolyl)-2-azetidinone 
• 622-97-9 1-ethenyl-4-methylbenzene 
• 402827-98-9 1-butyryloxymethyl-4-(p-tolyl)-2-azetidinone 
• 402827-97-8 1-hydroxymethyl-4-(p-tolyl)-2-azetidinone 

Relevant academic research and scientific papers

RETRACTED ARTICLE: Site-selective enzymatic C-H amidation for synthesis of diverse lactams

A major challenge in carbon?hydrogen (C?H) bond functionalization is to have the catalyst control precisely where a reaction takes place. In this study, we report engineered cytochrome P450 enzymes that perform unprecedented enantioselective C?H amidation reactions and control the site selectivity to divergently construct b-, g-, and d-lactams, completely overruling the inherent reactivities of the C?H bonds. The enzymes, expressed in Escherichia coli cells, accomplish this abiological carbon?nitrogen bond formation via reactive iron-bound carbonyl nitrenes generated from nature-inspired acyl-protected hydroxamate precursors. This transformation is exceptionally efficient (up to 1,020,000 total turnovers) and selective (up to 25:1 regioselectivity and 97%, please refer to compound 2v enantiomeric excess), and can be performed easily on preparative scale.

Comparison of separation performances of amylose- and cellulose-based stationary phases in the high-performance liquid chromatographic enantioseparation of stereoisomers of β-lactams

High-performance liquid chromatographic methods were developed for the separation of the enantiomers of 19 β-lactams. The direct separations were performed on chiral stationary phases containing either amylose-tris-3,5- dimethylphenyl carbamate, (Kromasil

A new route to enantiopure β-aryl-substituted β-amino acids and 4-aryl-substituted β-lactams through lipase-catalyzed enantioselective ring cleavage of β-lactams

A simple and efficient direct enzymatic method was developed for the synthesis of 4-aryl-substituted β-lactams and the corresponding β-amino acid enantiomers through the CAL-B (lipase B from Candida antarctica)-catalyzed enantioselective (E > 200) ring cleavage of the corresponding racemic β-lactams with 1 equiv. of H2O in i-Pr2O at 60°C. The product (R)-β-amino acids (ee ≥ 98%, yields ≥ 42%) and unreacted (S)-β-lactams (ee ≥ 95%, yields ≥ 41%) could be easily separated. The ring opening of enantiomeric β-lactams with 18% HCl afforded the corresponding enantiopure β-amino acid hydrochlorides (ee ≥ 99%).

Molecular Basis for the Enantioselective Ring Opening of β-Lactams Catalyzed by Candida antarctica Lipase B

Lipase B from Candida antarctica (CAL-B) catalyzes the slow, but highly enantioselective (E>200), ring-opening alcoholysis of two bicyclic and two 4-aryl-substituted β-lactams. Surprisingly, the rate of the reaction varies with the nature of the alcohols and was fastest with either enantiomer of 2-octanol. A 0.5-g scale reaction with 2-octanol as the nucleophile in diisopropyl ether at 60°C yielded the unreacted β-lactam in 39-46% yield (maximum yield is 50%) with ≥96% ee. The product β-amino acid esters reacted further by polymerization (not isolated or characterized) or by hydrolysis due to small amounts of water in the reaction mixture yielding β-amino acids (7-11% yield, ≥96% ee). The favored enantiomer of all four β-lactams had similar 3-D orientation of substituents, as did most previously reported β-lactams and β-lactones in similar ring-opening reactions. Computer modeling of the ring opening of 4-phenylazetidin-2-one suggests that the reaction proceeds via an unusual substrate-assisted transition state, where the substrate alcohol bridges between the catalytic histidine and the nitrogen of the β-lactam. Computer modeling also suggested that the molecular basis for the high enantioselectivity is a severe steric clash between Ile189 in CAL-B and the phenyl substituent on the slow-reacting enantiomer of the β-lactam.

Synthesis of 4-aryl-substituted β-lactam enantiomers by enzyme-catalyzed kinetic resolution

Enantiopure 4-phenyl- and 4-(p-tolyl)-2-azetidinones 3a, 3b, 4a and 4b (with e.e.s of ≥96%) were prepared through lipase-catalyzed asymmetric butyrylation of the primary OH group of N-hydroxymethylated β-lactams (±)-5 and (±)-6 at the (R)-stereogenic centre or by lipase-catalyzed asymmetric debutyrylation of O-butyryloxymethyl-2-azetidinones (±)-7 and (±)-8 at the (R)-stereogenic centre. The ring-opening of lactams 5a, 5b, 6b and 8a with HCl/EtOH afforded the corresponding β-amino ester enantiomers 9a, 9b, 10a and 10b with e.e.s of ≥92%.