1309945-57-0Relevant academic research and scientific papers
Amidation reactions from the direct coupling of metal carboxylate salts with amines
Goodreid, Jordan D.,Duspara, Petar A.,Bosch, Caroline,Batey, Robert A.
, p. 943 - 954 (2014/03/21)
A general method for the synthesis of amides involving the direct coupling of alkali metal carboxylate salts with amines is described. Amidation of a wide variety of carboxylate salts with either free amines or their ammonium hydrochloride salts can be achieved using HBTU as a coupling agent in combination with Huenig's base. The reaction is highly efficient and is generally complete in as little as 1-2 h, giving the products in good to excellent yields. The protocol is valuable for the coupling of carboxylates for which the corresponding carboxylic acids or acyl chlorides are unstable, less conveniently manipulated/isolated, or are not commercially available. For example, the coupling of amines and α-amino acids with lithium 5-bromo-1H-pyrrole-2-carboxylate, whose corresponding acid that is prone to decarboxylation, allowed for the synthesis of 5-bromo-1H-pyrrole-2-carboxamides, which are analogues of the pyrrole-2-aminoimidazole marine alkaloids. The protocol can be combined with other reactions in a sequenced fashion, as exemplified by the synthesis of acetylenic amides, in a one-pot procedure, via the coupling of a lithium carboxylate salt formed initially by the addition of carbon dioxide to a lithiated terminal alkyne.
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.
body text, 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.
