131432-92-3Relevant academic research and scientific papers
Kinetic resolution of α-bromoamides: Experimental and theoretical investigation of highly enantioselective reactions catalyzed by haloalkane dehalogenases
Westerbeek, Alja,Szymanski, Wiktor,Wijma, Hein J.,Marrink, Siewert J.,Feringa, Ben L.,Janssen, Dick B.
experimental part, p. 931 - 944 (2011/06/19)
Haloalkane dehalogenases from five sources were heterologously expressed in Escherichia coli, isolated, and tested for their ability to achieve kinetic resolution of racemic α-bromoamides, which are important intermediates used in the preparation of bioactive compounds. To explore the substrate scope, fourteen α-bromoamides, with different Cα- and N-substituents, were synthesized. Catalytic activity towards eight substrates was found, and for five of these compounds the conversion proceeded with a high enantioselectivity (E value >200). In all cases, the (R)-α-bromoamide is the preferred substrate. Conversions on a preparative scale with a catalytic amount of enzyme (enzyme:substrate ratio less 1:50 w/w) were all completed within 17-46 h and optically pure α-bromoamides and α-hydroxyamides were isolated with good yields (31-50%). Substrate docking followed by molecular dynamics simulations indicated that the high enantioselectivity results from differences in the percentage of the time in which the substrate enantiomers are bound favourably for catalysis. For the preferred (R)-substrates, the angle between the attacking aspartate oxygen atom of the enzyme, the attacked carbon atom of the substrate, and the displaced halogen atom, is more often in the optimal range (>157°) for reactivity. This can explain the observed enantioselectivity of LinB dehalogenase in a kinetic resolution experiment.
A simple enantioconvergent and chemoenzymatic synthesis of optically active α-substituted amides
Szymanski, Wiktor,Westerbeek, Alja,Janssen, Dick B.,Feringa, Ben L.
supporting information; experimental part, p. 10712 - 10715 (2011/12/05)
Simple and efficient: The combination of an enzymatic, enantioinverting reaction with simple follow-up processes allows the transformation of readily available racemic compounds into versatile chiral α-substituted amides (see picture; Ms=methanesulfonyl).
Lipase catalysed synthesis of optically enriched α-haloamides
Azim, Abul,Sharma, Sunil K.,Olsen, Carl E.,Parmar, Virinder S.
, p. 1345 - 1348 (2007/10/03)
An efficient lipase catalysed synthesis of optically enriched α-halogenated amides with concomitant optical enrichment of the starting α-haloesters is described. Candida antarctica lipase (CAL) was found to be a better catalyst over porcine pancreatic lipase (PPL) and Candida cylindracea lipase (CCL). The effect of different organic solvents was also studied.
Enantioselective synthesis of α-bromo acid derivatives and bromohydrins from tartrate derived bromoacetals
Boyes, Scott A.,Hewson, Alan T.
, p. 2759 - 2765 (2007/10/03)
Bromination of the acetals 4 derived from aryl alkyl ketones, ArCOR, and (2R,3R)-tartaric acid results in bromoacetals 5 with 78-90% de. Hydrolysis of those compounds with Ar = 4-methoxyphenyl or 3-bromo-4-methoxyphenyl results, after recrystallisation, in α-bromoketones 8 with 66-98% ee which are shown to undergo the Baeyer-Villiger oxidation to α-bromoesters 9 with minimal racemisation, α-Bromoketone 8d is shown to undergo carbonyl reduction to threo-bromohydrin 15 with retention of stereochemistry.
