70591-23-0Relevant academic research and scientific papers
An efficient procedure for the preparation of 4-substituted 5-aminoimidazoles
McLaughlin, Mark,Mohareb, Rafat M.,Rapoport, Henry
, p. 50 - 54 (2007/10/03)
The preparation of O-methylimidates from α-aminonitriles and their subsequent co-cyclization with primary amines to afford 4-substituted 5-aminoimidazoles was studied. It was found that the mildly acidic pyridinium p-toluenesulfonate efficiently catalyzed each stage of the reaction sequence: (a) the formation of the O-methylimidates, (b) their co-cyclization with a variety of primary amines, and (c) certain derivatizations of the resultant heterocycles. The developed reaction conditions tolerate a wide variety of α-aminonitriles and primary amine co-reactants. Thus, it is possible to easily prepare a diverse array of substituted heterocyclic compounds in good yield. The requisite α-aminonitriles were synthesized either from amino acids or by phase-transfer alkylation of a glycine anion equivalent. The unstable free 5-aminoimidazoles were normally protected in situ to provide derivatives (methyl imidates or N,N-dimethylamidines) that were amenable to characterization.
The enzymatic synthesis of isotopically labelled penicillin Ns with isopenicillin N synthase
Baldwin, Jack E.,Adlington, Robert M.,Crouch, Nicholas P.,Pereira, Ines A.C.
, p. 1145 - 1163 (2007/10/03)
The preparation of isotopically labelled penicillin Ns using a chemico-enzymatic approach is described. This route involves the chemical synthesis of variously labelled D,L,D,-aminoadipoyl-cysteinyl-valine tripeptides via well established facile protocols and concludes with the conversion of these tripeptides directly into penicillin Ns by the action of recombinant isopenicillin N synthase. Milligram quantities of isotopically labelled penicillin Ns, which would otherwise represent very challenging and expensive synthetic targets, are readily accessible from this route.
Cephalosporin biosynthesis: A branched pathway sensitive to an isotope effect
Baldwin,Adlington,Crouch,Schofield,Turner,Aplin
, p. 9881 - 9900 (2007/10/02)
Incubation of penicillin N (3a) with partially purified deacetoxy/deacetylcephalosporin C synthase (DAOC/DAC synthase) from Cephalosporium acremonium CO 728 gave in addition to the expected products, deacetoxycephalosporin C and deacetylcephalosporin C, a third β-lactam metabolite as a 3β-hydroxy-3α-methylcepham (9a). Production of the 3β-hydroxycepham was promoted from [3-2H]penicillin N (3b) which was rationalised by the operation of a kinetic isotope effect on a branched pathway in the enzymic process. The oxygen of the 3β-hydroxy group was shown to be derived in part from molecular oxygen. In addition, the 2β-methyl group of penicillin N was shown to be incorporated into C2 of the 3β-hydroxy-3α-methylcepham, a result in stereochemical accord with the equivalent transformation of the 2β-methyl group of penicillin N into C2 of deacetoxycephalosporin C1. A mechanistic interpretation, consistent with these observations, is offered.
